IBC Cells Research Articles

Plasma‐Enhanced Chemical‐Vapor‐Deposited SiOx(Ny)/n‐type Polysilicon‐on‐Oxide‐Passivating Contacts in Industrial Back‐Contact Si Solar Cells

In this article, different in situ grown plasma‐enhanced chemical vapor deposition (PECVD)‐grown interfacial oxides for n‐type polysilicon‐passivating contacts are investigated. Herein, SiOx(Ny)/n‐type amorphous silicon stacks created from either N2O plasma or O2 plasma are applied to POLy‐silicon on Oxide interdigitated back‐contact (POLO IBC) solar cells using the structured deposition process through a glass mask to create the IBC layout. The impact of plasma exposure time for interfacial oxide growth on solar cell efficiencies is experimentally determined. In the POLO IBC cell results, it is shown that the PECVD oxides SiOxNy and SiOx with optimized plasma exposure time give similar maximum efficiencies of 23.8% and 23.7%, respectively. In these data, the feasibility to deposit a high‐quality in situ PECVD interfacial SiOx(Ny) layers for surface passivation and current transport of passivated contacts at the same time is demonstrated. For the SiOx/n‐type polysilicon stack, it is found that both plasma exposure time for interfacial oxide growth and polysilicon anneal temperature variations can lead to similar optimum of solar cell efficiencies. The current open‐circuit voltage losses due to metallization for the solar cells are analyzed and a realistic efficiency of 25.22% is calculated to achieve optimized POLO IBC solar cells applying the synergistic efficiency gain analysis on Quokka3 simulations.

Abstract PO3-26-12: Targeting Lipocalin-2 in HER2+ Inflammatory Breast Cancer Using Herceptin-Conjugated Liposomes

Abstract Inflammatory breast cancer (IBC) is a rare and aggressive subtype of BC that accounts for 1 to 5% of all types of BC. Due to its inflammatory characteristics and the absence of a palpable mass, IBC is usually confounded with a mastitis. Unfortunately, once properly diagnosed, IBC has already metastasized. A high portion of IBC tumors overexpress human epidermal growth factor receptor 2 (HER2). These IBC patients (HER2+) are treated with Trastuzumab, a monoclonal antibody. However, many IBCs become resistant to this therapy. Thus, there is not an optimal treatment against this horrendous disease. One potential target against IBC is Lipocalin-2 (LCN2), a secreted protein involved in iron homeostasis, immune responses, transport of siderophores, and epithelial cell differentiation. In many aggressive tumors, high levels of LCN2 have been associated with increased cancer cell motility, proliferation, angiogenesis, invasion, and metastasis. LCN2 is aberrantly abundant in IBCs compared with non-IBC patients and cell lines. This information indicates that LCN2 could be a target for IBC therapy. Our research team showed that small interference RNAs (siRNAs) targeting LCN2 effectively reduced the cell proliferation and invasion ability of IBC cells. To systemically deliver siRNA specifically to HER2+ IBC cells, we prepared Herceptin-conjugated liposome loaded with siRNA against LCN2. Trastuzumab conjugated liposomes werecharacterized by using dynamic light scattering to measure the size distribution and the zeta potential. Our formulation displayed sizes of 18.3 and 73.7 nm which could correspond to free DSPE-PEG-(2000) trastuzumab and the trastuzumab-liposome, respectively. To determine the optimal timepoint of liposome internalization into IBC cell lines, we incubated HER2+ IBC3 cells with liposomes for different time-points. Optimal internalization was observed at 24 and 48-hr. To further understand the downstream effectors of LCN2 in IBC cells, we performed RNAseq in siRNA-mediated LCN2 knockdown cells. Further bioinformatics with the RNAseq data, revealed 138 dysregulated genes following LCN2 knockdown as compared with a negative control (NC) siRNA. Particularly, increased STAT1 levels has been associated with to distant metastasis and poor clinical prognosis in cancer. In our study, STAT1 levels decreased after LCN2 silencing. Ingenuity Pathway Analysis (IPA) showed 25 canonical pathways altered in the LCN2 knockdown cells as compared with the NC-siRNA. These results indicate that LCN2 activate molecular pathways involved in cell proliferation, invasion and metastasis in IBC cells. Citation Format: Marienid Flores-Colón, Pablo Vivas-Rivera, Pablo E. Vivas-Mejía. Targeting Lipocalin-2 in HER2+ Inflammatory Breast Cancer Using Herceptin-Conjugated Liposomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-26-12.

Abstract 6951: The role of estrogen-dependent activation of p38 MAPK signaling pathway in inflammatory breast cancer

Abstract Inflammatory breast cancer (IBC) is a rare and aggressive type of breast cancer in which the lymphatic vessels become blocked by cancer cells in the breast tissue. The five-year survival rate for this type of cancer is around 40%, one of the worst among breast cancer. Most IBCs are estrogen receptor (ER) and progesterone receptor (PR) negative and HER2 positive, with some presenting an amplification of HER2 while others are ER, PR, and HER2 negative, formally known as the triple-negative (TNBC) subtype. However, it has been reported that treatment with 17β-Estradiol (E2) of ER-negative IBC and non-IBC cells can exert rapid non-genomic signaling mediated by ERα-36, GPR30, and/or estrogen receptor beta, activating MAPK pathways involved in oncogenic phenotypes. Previous data generated in our lab showed that when cells were treated with estradiol it led to increased phosphorylation levels of p38. However, the specific role p38 MAPK signaling takes on in IBC is unknown. Thus, this study centers on examining the role of estradiol and p38 regulation in the triple-negative IBC cell line model, SUM149PT. We hypothesize that upon estradiol treatment p38 signaling pathway is activated resulting in the over-expression of pro-inflammatory cytokines which regulate pro-tumorigenic phenotypes including the growth and survival of IBC cells. Inflammatory cytokines can promote pro-oncogenic features by promoting cell proliferation, angiogenesis, and immune suppression. We treated SUM149 IBC cells with 10nM of estradiol and measured the levels of human cytokines using a Human Cytokine Antibody Array. In addition, treatment using SB202190, a potent p38 inhibitor, caused a significant decrease in cell viability of several breast cancer cell lines in a dose-dependent manner. Ongoing studies include assessing the effects of p38 inhibition proliferation, invasion, and migration. In summary, a better characterization of the effect of E2 and p38 activation in ER-negative cell lines may provide great insight into novel targeted therapies for IBC. Citation Format: Keyla V. Ramirez, Adrian D. Bonilla-González, Jeisac Guzman-Rivera, Esther A. Peterson-Peguero. The role of estrogen-dependent activation of p38 MAPK signaling pathway in inflammatory breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6951.

Abstract 3171: The effect of estrogen and phytoestrogens in Inflammatory breast cancer

Abstract Inflammatory breast cancer is an aggressive and lethal type of breast cancer. Frequently, this cancer is diagnosed in an advanced stage with metastasis. IBC diagnosis is associated with a worse survival rate than other types of breast cancer. The presence of dermal and stromal tumor emboli blocking the lymphatic vessels under the skin is considered a hallmark of IBC and assumed to be responsible for the high metastatic behavior and aggressiveness of IBC disease. To this date, there are no effective targeted therapeutics, especially for those patients that account for approximately 20-40% of IBC cases with triple-negative breast cancer (TNBC) classification. Several studies have shown that estrogen can exert non-genomic effects in IBC and non-IBC TNBC, mediated by the expression of alternate estrogen receptors including estrogen receptor alpha-36, and GPR30. In this context, estrogen can activate non-genomic signaling pathways involved in the acquisition of oncogenic phenotypes such as increased motility and invasion in IBC cells. Phytoestrogens, naturally derived structural analogs to 17β-estradiol (E2), were evaluated as an alternative treatment option using in vitro IBC cell models (SUM149 and SUM190). Given the estrogenic properties of phytoestrogens, the drugs were hypothesized to interact with targets in pathways similar to E2 in non-genomic signaling. Several phytoestrogens including coumestrol (Cou) can induce a cytotoxic effect in TNBC. We hypothesize (1) that estrogen non-genomic signaling has an active role in the aggressive metastatic phenotype of IBC, and (2) that Cou has anticancer activity by inhibiting estrogen non-genomic signaling in IBC. To test these hypotheses, IBC cells were treated with E2 or Cou to determine their effects on the activation of downstream kinases by western blot and phospho-kinase array assays. In addition, transcriptional effects upon treatment with Cou were identified using RNA-seq. A dose-response curve in 2D and 3D models was generated to determine the half-maximal inhibitory concentration (IC50) of Cou. Finally, treatment using the IC50 of Cou caused a decrease in cell viability in the TNBC cell line. Also, in comparison to E2, Cou decreases migration, proliferation, and tumor emboli formation in IBC cell lines. In addition, IBC cells were treated using monotherapy and combination therapy with phytoestrogens including Cou, genistein (GN), and/or 8-prenylnaringenin (8-PN). Observed reductions of cell viability in IBC cell lines treated with the different phytoestrogens and combinations make them worthy of further characterization as anti-cancer therapies in in vitro and in vivo models. In summary, IBC cells are responsive to E2 making this signaling pathway attractive for the development of innovative therapeutic strategies with phytoestrogens as potential candidates for treatment. Citation Format: Esther A. Peterson-Peguero, Keishla Rodriguez-Martir, Madeline Ganshert, Dalissa Negron-Figueroa, Ayeisha N. Colon-Ortiz. The effect of estrogen and phytoestrogens in Inflammatory breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3171.

Abstract 6270: Anti-metastatic effects of estrogen receptor β in inflammatory breast cancer

Abstract Inflammatory breast cancer (IBC) is a rare but highly aggressive form of breast cancer with a 5-year survival rate of less than 50%. Although 20-30% of women with IBC have distant metastasis at the time of diagnosis, the biology underlying the aggressive behavior of the disease is poorly understood and molecular markers that distinguish IBC from non-IBC have not yet been identified. In response to the urgent need of discovering new targeted therapies in IBC, we have studied the second estrogen receptor (ERβ) since prior work from our lab correlated higher tumor expression of ERβ in samples from IBC patients with longer metastasis free survival. We showed that ERβ exerted anti-metastatic activity in IBC by inhibiting actin-based cell migration through the suppression of RhoC GTPase signaling. However, since estrogen receptors elicit their effects by inducing global cellular alterations, we have now adopted an integrated genomic approach to fully understand the anti-metastatic effects of ERβ in IBC and delineate the underlying transcriptional regulatory circuits. We found ERβ binding sites in IBC cells and combined this information with gene expression data to identify downstream direct target genes and associated pathways. Our findings suggest the regulation of tumor micro-environment and metabolism as the primary targets of ERβ and we are currently working to pinpoint the crucial regulatory components in these functions. Our findings thus offer an opportunity to better understand the mechanism of ERβ action in aggressive breast cancer, serving as a critical step in validating its tumor repressive role. Citation Format: Harika Nagandla, Spyros Tastsoglou, Kim Cuong Cap, Aireana Phillips, Wei Qian, Jianying Zhou, Jenny Chang, Savitri Krishnamurthy, Naoto Ueno, Artemis Hatzigeorgiou, Christoforos Thomas. Anti-metastatic effects of estrogen receptor β in inflammatory breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6270.

Evaluating the Practical Efficiency Limit of Silicon Heterojunction–Interdigitated Back Contact Solar Cells by Creating Digital Twins of Silicon Heterojunction Solar Cells with Amorphous Silicon and Nanocrystalline Silicon Hole Contact Layers

Improving power conversion efficiency (PCE) in photovoltaics has driven innovative approaches in solar cell design and technology. Silicon heterojunction (SHJ) solar cells exhibit advantages in PCE due to their effective passivating contact structures. SHJ–interdigitated back contact (SHJ–IBC) solar cells have the potential to surpass traditional SHJ cells, attributed to their advantage in short‐circuit current (JSC). Herein, Silvaco Atlas technology computer‐aided design is used to create digital twins of high‐efficiency SHJ solar cells with amorphous silicon and nanocrystalline silicon hole selective contact (HSC) layers. Using parameters from digital twins of SHJ solar cells, the practical efficiency limit of SHJ–IBC solar cells is assessed. The results show that SHJ–IBC cells can achieve potential efficiencies of 27.01% with amorphous HSC and 27.38% with nanocrystalline HSC. Further efficiency augmentation to 27.51% can be achieved by narrowing the gap from 80 to 20 μm. This study not only advances comprehension of SHJ–IBC solar cells but also provides insights into optimizing geometrical configurations for improved performance. The utilization of digital twins provides a valuable tool for predicting and evaluating the performance of SHJ–IBC solar cells, contributing substantively to the ongoing development of high‐efficiency photovoltaic technology.

Abstract B013: Understanding the anti-metastatic activity of estrogen receptor β in inflammatory breast cancer

Abstract Inflammatory breast cancer (IBC) is a highly metastatic breast carcinoma with high frequency of estrogen receptor a (ERα) negativity. We previously explored the second ER subtype, (ERβ) and reported expression in IBC tissues and correlation with reduced metastasis in patients. We have also seen decreased metastasis of IBC tumors in vivo when ERβ was expressed or activated by agonists. Mechanistically, we found that ablation of ERβ in IBC cells increased actin-based cell migration and activated gene expression that promote Rho GTP signaling and cytoskeleton reorganization. Because migratory cells undergo metabolic and epigenetic adaptations that enable them to evade immune surveillance and progress to metastasis, we have now followed an integrated approach to fully understand the role of ERβ as a driver of interconnected transcriptional programs that function to inhibit aggressive phenotypes. We have mapped ERβ binding sites in IBC cells and interrogated this information with gene expression data to identify downstream targets that prevent IBC cells from gaining metastatic traits. Through analysis of cells that express endogenous ERβ and upon its activation by agonists we have defined how a physiologically relevant receptor interacts with the cancer genome to adjust differentiation, metabolism and tumor host interactions to mitigate the metastatic propensity of IBC cells. We compared target genes in normal and malignant tissues and associated their expression with clinical outcomes to strengthen their biological relevance and evaluate their potential use as molecular targets. Our findings thus offer ample opportunities to advance our understanding about endocrine mechanisms that operate within the tumor microenvironment to regulate metastasis with the potential to discover novel targets for therapy intervention. Citation Format: Ilias Karagounis, Spyros Tastsoglou, Harika Nagandla, Naoto Ueno, Amit Maity, Artemis Hatzigeorgiou, Christoforos Thomas. Understanding the anti-metastatic activity of estrogen receptor β in inflammatory breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B013.

Abstract 3635: TBK1 inhibition potentiates the efficacy of AXL-targeted therapy by modulating tumor microenvironment in aggressive breast cancers

Abstract Introduction: Triple-negative and inflammatory breast cancer (TNBC and IBC) are the most aggressive breast cancer subtypes. Novel actionable targets and complementary therapies are critically needed. AXL, a receptor tyrosine kinase, drives pleiotropic phenotypes of TNBC and IBC aggressiveness. Targeting AXL reduces IBC tumor growth in vivo and inhibits polarization of M2 macrophages. To identify novel tumor microenvironment (TME) targets to enhance the efficacy of AXL-targeted therapy, we conducted a synthetic lethal kinome siRNA screening. We identified TBK1 as a candidate to synergize with AXL growth inhibition. TBK1 is a serine/threonine protein kinase that regulates innate, adaptive responses and antitumor immune responses. We hypothesized that inhibition of TBK1 enhances the antitumor effect of AXL-targeted therapy in aggressive breast cancers. Methods: We used knockdown, knockout (KO) and inhibitors to suppress AXL and TBK1 pathways and tested the synergistic effect of targeting AXL and TBK1 on the growth of human SUM149 and BCX010 IBC cells, and HS578T TNBC cells in vitro. To determine the synergistic effect of targeting both pathways in vivo, we inoculated control or TBK1 KO murine TNBC 4T1.2 cells into BALB/c mice. We assessed the activity of AXL inhibitor TP-0903 in reducing tumor growth. Using multicolor flow cytometry, we studied the effects of targeting AXL and TBK1 on the TME. We tested the activity of TP-0903 combined with a TBK1 inhibitor in another TNBC mouse model, E0771. We used RNA-sequencing and real-time PCR/Western blot to determine the molecular mechanisms of how TBK1 inhibition synergizes AXL-targeted therapy in these cancers. Results: Compared with AXL or TBK1 suppression alone, genomic or pharmacologic suppression of AXL and TBK1 significantly reduced the growth of SUM149, BCX010, and HST578T cells in vitro. In both 4T1.2 and E0771 syngeneic mouse models, TP-0903 was more active in reducing tumor growth in TBK1-inhibited tumors than in control tumors. Tumors with TBK1 inhibition and treated with TP-0903 had a significantly higher population of cytotoxic T cells than control tumors. Depletion of CD8+ T cells blocked the synergistic effect of targeting AXL and TBK1 pathways on reducing tumor growth, suggesting that cytotoxic T cells contributed to the anti-tumor synergy of targeting AXL and TBK1. Mechanistically, TBK1 induced M2 macrophage migration via IRF3-regulated CCL5 secretion in SUM149 and HS578T cells, and AXL KO attenuated the polarization and migration of M2 macrophages by inhibiting the CCR5/CCL5 axis. Conclusions: Targeting TBK1 enhances the efficacy of AXL-targeted therapy in aggressive breast cancer by suppressing the paracrine effect of CCR5/CCL5 axis. This combination represents a novel and effective therapy modulating the TME of aggressive breast cancer, which warrants further investigation in the clinical setting. Citation Format: Lan Phi, Takashi Semba, Ngu V. Trinh, Fang Zou, Jason M. Foulks, Steven L. Warner, Savitri Krishnamurthy, James P. Long, James M. Reuben, Debu Tripathy, Naoto T. Ueno, Xiaoping Wang. TBK1 inhibition potentiates the efficacy of AXL-targeted therapy by modulating tumor microenvironment in aggressive breast cancers. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3635.

Abstract P2-26-15: CCR7 expression in Inflammatory breast cancer

Abstract Background: Inflammatory breast cancer is an aggressive breast cancer characterized by florid congestion of lymphovascular spaces by tumor emboli. CCR7 is an immune cell receptor that mediates traffic of immune cells into lymphatics that can be expressed on tumor cells. An RNA-seq screen of tumor promoting mammary glands in mice identified CCR7 as an upregulated signal in mammary glands that promoted IBC-like skin invasion. We examined the expression of CCR7 in IBC cell lines and patients to determine the prevalence of this receptor in IBC. Methods: Protein lysates from IBC and non-IBC cell lines were subjected to immunoblotting using anti CCR7 (R&D systems). An IBC tissue microarray from post-chemotherapy mastectomy specimens of 39 patients, each with three replicates was subjected to immunohistochemical staining for CCR7 (Invitrogen, catalog number MA5-31992) performed using a Leica Bond RX autostainer with an incubation time of 60 minutes at 1:15,000 after 20 minutes of heat-induced antigen retrieval at pH 6.0. In 15 cases there were no tumor cells observed in the cores. Staining was scored by an expert breast pathologist for intensity and percent tumor stained. Staining patterns were scored. Descriptive statistics were examined for representation by receptor subtype. Results: CCR7 staining was strong in all lines examined including MCF7, SUM149, SUM190, MDA-IBC, and SUM159. Among 24 IBC patient cores with tumor in the tissue, 23 (96%) expressed CCR7 in tumor, 15 with complete membranous staining and 9 with incomplete membranous staining. In one case with LVSI the emboli were CCR7 positive. Among the 24 positive cases, 22 were 3+ intensity while two were 2+. Nine CCR7+ cases were estrogen receptor (ER) ER+, 8 ER-, and 6 unknown. HER2 status is pending. Conclusions: CCR7 expression is present across tumor subtypes in IBC cell lines and in both ER+ and ER- patient tumors. Given developing novel pharmacologic targeting of CCR7, this target warrants further investigation in IBC and other breast cancers. Citation Format: Wintana Balema, Savitri Krishnamurthy, Alison Lawrence, Megan Rodriguez, Richard Larson, Natalie Fowlkes, Naoto T. Ueno, Wendy Woodward. CCR7 expression in Inflammatory breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-15.

Abstract 974: Genome-wide analysis of estrogen receptor b binding sites: Implications for endogenous anti-metastatic activity in inflammatory breast cancer

Abstract Inflammatory breast cancer (IBC) is a highly metastatic breast carcinoma with high frequency of estrogen receptor a (ERa) negativity. We previously explored the second ER subtype, (ERb) and reported expression in IBC tumors and its correlation with reduced metastasis in patients. We have also seen decreased metastasis of IBC tumors when ERb is expressed or activated by chemical agonists. In contrast, ablation of ERb in IBC cells increased migration and stimulated signaling pathways that activate Rho GTPases promoting actin reorganization. We have now mapped all ERb binding sites in IBC cells and by interrogating this information together with gene expression data we identified genomic targets that mediate its tumor repressive effects. Through a combined analysis of cells that express endogenous ERb and knockout cells engineered to re-express the receptor we have defined how a biologically relevant ERb interacts with the cancer cell genome to control metastatic signals in IBC. We reveal key binding motifs and cis-regulatory chromatin sites and associate target genes with clinical outcomes to strengthen the relevance of ERb signaling for the progression of IBC. Our findings thus offer an opportunity to better understand the mechanism of ERb action that is critical step in validating its tumor repressive role in breast cancer. Citation Format: Ilias V. Karagounis, Spyros Tastsoglou, Anna Karavangeli, Amit Maity, Artemis Chatzigeorgiou, Christoforos Thomas. Genome-wide analysis of estrogen receptor b binding sites: Implications for endogenous anti-metastatic activity in inflammatory breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 974.

Towards 28 %-efficient Si single-junction solar cells with better passivating POLO junctions and photonic crystals

We conduct numerical device simulations to study to what extend poly-Si on oxide (POLO)2 IBC solar cells can be optimized. In particular, we evaluate the benefit of the concept of photonic crystals (PCs) for “standard” cell thicknesses compatible with industrial wafer handling. We find that for our current surface passivation quality, implementing PCs and decreasing the wafer thickness down to 15 μm would increase the efficiency by „only“ 1% absolute due to limiting surface recombination losses. We deduce a high c-Si/SiOx interface state density Dit of 2.9 × 1012 eV−1cm−2 by analyzing special two-terminal IV measurements on small pads that contact the intact interfacial oxide between pinholes with our MarcoPOLO model. Consequently, we improve the hydrogenation process of our POLO junctions by an Al2O3/SiNx/Al2O3 rear-side dielectric layer stack. For n-type POLO (p-type POLO) J0 is reduced from 4 (10) fA/cm2 down to 0.5 ± 0.3 (3.3 ± 0.7) fA/cm2. For this improved surface passivation, our numerical device simulations predict an efficiency potential of 29.1% (27.8%) for POLO2 IBC cells with (without) PCs for a standard thickness of 150 μm. This shows that the “practical limit” for Si solar cells with poly-Si on oxide-based passivating contact schemes is above 27%, and, in general, that the efficiency potential of Si single-junction cells is still far from being exhausted. The first implementation of the improved POLO junctions into cell precursors confirms the predicted improvement on the level of suns - implied open-circuit voltage curves.

Molecular Mechanism by which Coumestrol Exerts its Anticancer Activity in Triple‐Negative Inflammatory Breast Cancer

Coumestrol (Cou) is a phytoestrogen present in soy and clover sprouts which is structurally similar to estrogen (E2) and has a cytotoxic effect in breast cancer cell lines. Nevertheless, the molecular mechanism by which Cou can exert its effect in the most aggressive breast cancer subtype, triple‐negative inflammatory breast cancer (TN‐IBC), is still unknown. Several studies show that TN‐IBC cell lines are unresponsive to hormonal therapies, but E2 can activate signaling pathways involved in pro‐oncogenic phenotypes such as motility and invasion. Therefore, the objective of this study was to determine if Cou has an anti‐cancer effect in TN‐IBC cell lines and the molecular mechanism that Cou exerts for its anti‐cancer activity using 2D cell culture models. For this, a dose‐response curve of Cou in 2D models of TN‐IBC cell lines was generated to determine the half‐maximal inhibitory concentration (IC50). Also, relative cell viability was performed in ER‐positive, triple‐negative, TN‐IBC, and HER2‐amplified IBC cell lines. Functional assays were performed in TN‐IBC cell lines to determine the effect of E2 alone, Cou alone, and in a combination of treatments on cell viability, migration, and invasion. Also, the effect on phosphorylation of downstream kinases was analyzed by a proteome profile human phospho‐kinase array. An RNA‐seq was performed in TN‐IBC cell lines to identify transcriptome changes after Cou treatment. Preliminary observations demonstrated that Cou treatment using the IC50 (13µM) caused a decrease in cell viability in TN‐IBC cell lines. Similarly, Cou treatment reduces triple‐negative non‐IBC viability. Also, in comparison with E2, Cou decreases migration and invasion in TN‐IBC cell lines. Finally, Cou treatment reduces the phosphorylation of kinases that promote pro‐oncogenic phenotypes and upregulate genes involved in breast cancer phenotype suppression. In summary, the data gathered in this study will guide us in elucidating a signaling pathway affected by Cou’s anti‐cancer activity. More importantly, it will open the opportunities to design more effective targeted therapeutic strategies to improve the prognosis and survival rates of IBC patients.

Abstract P1-24-04: Spatially resolved cell type heterogeneity uncovers the distinct biology of inflammatory breast cancer

Abstract Inflammatory breast cancer (IBC) is the most lethal form of breast cancer due to rapid progression, distinct morbidity due to pain, swelling, infection and eventual death. It accounts for 10% of all breast cancer caused deaths despite being only 2-4% of all breast cancer diagnosis. Histopathologically, scattered tumor emboli and dermal lymphatic invasion are typical histopathological findings of IBC, shown in about 75% of all IBC cases. However, the etiology of this disease remains largely unknown and its diagnostic difficult to establish.Using single cell transcriptomics, we profiled a total of 10 patient-derived needle biopsies from IBC-hormone receptor (IBC-HR), IBC-triple negative breast cancer (IBC-TNBC), TNBC and HR subtypes, and one normal breast sample. After data QC, we obtained a total of 36,000 cells representing immune, epithelial and stromal cell populations. We performed analysis of the spatial cell distribution through a transcriptomics-informed panel using highly multiplex imaging mass cytometry (IMC) on FFPE section obtained from the same patients.While we noted interpatient heterogeneity within cancer cells in our single cell dataset, immune and stromal cells did show similarity across IBC patients. We identified differences across the myeloid compartment between IBC and non-IBC cells, specifically affecting the dendritic cell subpopulations.The interferon gamma pathway was specifically elevated in several cell types across IBC patients, and particularly in immune cells such as T and myeloid cells. We used MX1 as a marker of interferon gamma response as part of the IMC panel and confirmed this signature in IBC samples. There was no alpha and beta interferon transcriptomic signature in the single cells. Through IMC, we were able to identify the cellular composition surrounding the tumor microemboli. Contrary to what has been postulated in the literature, these cells are not lymphatic cells, but appear to be of fibroblastic origin and express the fibroblast marker CD90. As well, we detected a non-overlapping distribution of Collagen 1 positive and CD90 positive fibroblasts throughout the IBC specimens, revealing heterogeneity within the fibroblast population and its organization. Spatial immune cell analysis also revealed the presence of tertiary lymphoid structures in IBC tumors. Citation Format: Elise Courtois, William Flynn, Santhosh Sivajothi, Martine Seignon, Diane Luo, Bora Lim, Paul Robson. Spatially resolved cell type heterogeneity uncovers the distinct biology of inflammatory breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-24-04.

Commercial Solar Cells With Graphene Oxide as the Passivation Film

The negative fixed charge density contributed by graphene oxide is estimated as high as 6 x 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">12</sup> cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−2</sup> . Graphene oxide is therefore a promising candidate for Si solar cell passivation. However, the high-temperature steps for manufacturing commercial Si solar cells would change the composition of graphene oxide. Therefore, graphene oxide cannot be directly adopted by commercial PERC manufacturers with the high-temperature firing step after the rear passivation step. To suppress the high-temperature degradation, we have deposited the graphene oxide on the rear surface of commercial IBC cells directly, and V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">oc</sub> , J <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sc</sub> and efficiency of the cell all improved after 100 μL graphene oxide deposition. Graphene oxide can be adopted as the passivation material of commercial cells as long as the high-temperature process on graphene oxide can be suppressed.

Estrogen Receptor β-Mediated Inhibition of Actin-Based Cell Migration Suppresses Metastasis of Inflammatory Breast Cancer.

Inflammatory breast cancer (IBC) is a highly metastatic breast carcinoma with high frequency of estrogen receptor α (ERα) negativity. Here we explored the role of the second ER subtype, ERβ, and report expression in IBC tumors and its correlation with reduced metastasis. Ablation of ERβ in IBC cells promoted cell migration and activated gene networks that control actin reorganization, including G-protein-coupled receptors and downstream effectors that activate Rho GTPases. Analysis of preclinical mouse models of IBC revealed decreased metastasis of IBC tumors when ERβ was expressed or activated by chemical agonists. Our findings support a tumor-suppressive role of ERβ by demonstrating the ability of the receptor to inhibit dissemination of IBC cells and prevent metastasis. On the basis of these findings, we propose ERβ as a potentially novel biomarker and therapeutic target that can inhibit IBC metastasis and reduce its associated mortality. SIGNIFICANCE: These findings demonstrate the capacity of ERβ to elicit antimetastatic effects in highly aggressive inflammatory breast cancer and propose ERβ and the identified associated genes as potential therapeutic targets in this disease.

Abstract 5918: The role of the cell-adhesion molecule Metadherin in inflammatory breast cancer progression

Abstract Inflammatory breast cancer (IBC) is the most lethal form of breast cancer where patients display a lower 5-year survival rate. The lethality of IBC originates from its nature of invading the vascular and lymphatic systems, absence of a tumor mass, and generation of tumor emboli. Currently, the accurate and early diagnosis and the development of effective targeted therapies remains a challenge. Thus, in an attempt to discover potential biomarkers, we characterized the IBC cell surface proteome. Plasma membrane proteins were identified via SILAC and MS quantitative proteomics using the IBC SUM-149 vs. MCF-10A a non-cancerous mammary epithelial cell line. SILAC results showed overexpression of Metadherin (MTDH) in IBC cells (&amp;gt;2.0 FCh) and was validated in IBC tissues and emboli. MTDH is a cell adhesion molecule overexpressed in many cancer types, including breast cancer. MTDH promotes cancer progression by modulating various signaling pathways including NF-kB, which is related to cell survival, proliferation, invasion and metastasis. Thus, the aim of this study is to assess the functional role of MTDH in IBC progression. To elucidate the mechanism of action of MTDH in colony formation and tumor spheroids we silenced MTDH (CRISPR or shRNA) SUM-149 and SUM-190 IBC cells. We assessed the expression of MTDH by immunoblotting and immunofluorescence where we observed reduced MDTH levels. The number of colonies formed in SUM-149 MTDH silenced cells was ~40% lower when compared to non-silenced cells. Tumor spheroids of SUM-149 and SUM-190 MTDH silenced cells were smaller than non-silenced cells. Additionally, MTDH silencing results in a decrease in the phosphorylation of the p65 subunit of NF-kB while no changes are observed in total protein abundance in SUM-149 cells. We can conclude from our preliminary results that MTDH serves as a potential IBC target for IBC progression. This work was supported by NIH NIGMS #GM111171 (MMM), SGRP 2017-00143 (MMM and GOS), NIMHD #MD007583 (MMM), GM103475 (UPR MMM), Title-V-PPOHA #P031M105050, Title-V-Cooperative #P031S130068 from the U.S. Dept. of Education and Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health #P20GM103475 (GOS). Citation Format: Gabriela Ortiz-Soto, Ivette J. Suárez-Arroyo, Michelle M. Martínez-Montemayor. The role of the cell-adhesion molecule Metadherin in inflammatory breast cancer progression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5918.

Abstract 2951: Knockdown of SCAMP3 suppresses the proliferation and emboli formation capacity of inflammatory breast cancer cells through EGFR signaling

Abstract Inflammatory Breast Cancer (IBC) is one of the most lethal forms of breast cancer (BC), where patients have a 43% increased risk of death compared to women with non-IBC advanced BC. Approximately 30% of triple-negative (TN) IBC cases overexpress the Epidermal Growth Factor Receptor (EGFR). EGFR amplification is associated with a poor overall survival rate compared with EGFR-negative IBC cases. We previously identified increased expression of the secretory carrier membrane protein 3 (SCAMP3) in EGFR overexpressing TN SUM149 IBC cells, tissues and in the IBC metastasis promoting structure, the tumor emboli. SCAMP3 is an endosome-associated protein known to regulate the degradation of EGFR. Thus, we aim to elucidate the role of SCAMP3 in the regulation of EGFR signaling and IBC progression. To investigate how SCAMP3 contributes to the IBC cellular response, we knocked out (KO) the expression of SCAMP3 in IBC SUM149 cells using the CRISPR/Cas9 technique. Wild type (WT) and KO IBC cells treated with EGF for 30 min in serum-starved conditions were used to assess cell viability after 24, 48, 72, and 96h, colony, and emboli formation capacity. Our results demonstrate a reduction in the proliferation, colony, and emboli formation capacity of SCAMP3 KO cells in comparison with the WT. Taken together our results show that SCAMP3 plays a promoting role in the progression of IBC through EGFR signaling modulation. Citation Format: Ivette J. Suarez-Arroyo, Jael Reyes-Chea, Michelle M. Martinez-Montemayor. Knockdown of SCAMP3 suppresses the proliferation and emboli formation capacity of inflammatory breast cancer cells through EGFR signaling [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2951.

Abstract PD7-02: Estrogen receptor β suppresses metastasis of inflammatory breast cancer by regulating signaling that promotes cytoskeleton remodeling

Abstract Inflammatory breast cancer (IBC) is the most lethal form of breast cancer that accounts for about 10% of breast cancer mortality annually in US. Poor prognosis is largely due to the high propensity of IBC tumors to develop distant metastasis. Owing to the complex metastatic process, the molecular basis of IBC aggressiveness is poorly understood and no specific therapeutic target has been identified. Among the few signaling pathways that differ between IBC and non-IBC is the Rho GTPase that is hyperactivated in many IBC tumors and is associated with cell motility in IBC cells. However, Rho GTPases are not druggable factors and the pathways that activate these proteins in IBC are not fully defined. Another difference is that up to 83% of IBC tumors lack estrogen receptor α (ERα) expression compared with other forms of breast cancer that are mostly ERα-positive. Despite the lack of ERα in the majority of IBC tumors, estrogen may still play a role in these cancers through pathways that involve ERβ. Our tissue staining reveals expression of ERβ in a significant number of IBCs that is reproduced in IBC cell lines. Furthermore, analysis of IBC datasets indicates correlation of receptor expression with good prognosis. We studied this association in preclinical models of IBC by knocking out ERβ in IBC cells. This promotes migration and invasion through cytoskeleton remodeling whereas re-expression of the receptor in knockout cells restores the cytoskeletal structure and migration to the levels of control cells. Consistent with increased migration, deletion of ERβ activates large gene networks of cell de-differentiation including cell surface receptor signaling that enhances Rho GTPase activity to promote the motile phenotype of IBC cells. In contrast, ligands that activate ERβ inhibit the same signaling that contributes to metastasis in IBC. Analysis of orthotopic xenograft models shows that IBC tumors lacking ERβ have higher propensity for metastasis compared with the ERβ-proficient tumors. Conversely, ERβ agonists decrease the metastatic potential of IBC tumors supporting the anti-metastatic activity of the receptor. Our findings point towards a role of ERβ in preventing distant metastases by inhibiting dissemination of IBC cells. This function combined with distinct expression indicates the potential of ERβ to represent a unique prognostic marker and therapeutic target that can be utilized to repress IBC metastasis and eliminate its associated mortality. Citation Format: Christoforos Thomas, Ilias Karagounis, Ratnesh Srivastava, Sushil Kumar, Noelle Francois, Fotis Nikolos, Igor Bado, Hann-Hsiang Chao, Constantinos Koumenis, Savitri Krishnamurthy, Naoto T Ueno, Rumela Chakrabarti, Amit Maity. Estrogen receptor β suppresses metastasis of inflammatory breast cancer by regulating signaling that promotes cytoskeleton remodeling [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD7-02.

Abstract P3-03-03: Inflammatory breast cancer exhibits amplification and transcriptional activation of MYC in conjunction with NOTCH and TGFβ signaling

Abstract Inflammatory breast cancer (IBC) is an aggressive and poorly characterized breast cancer subtype with few targets available for molecular therapy. Several attempts aimed at characterizing the disease at the genomic, transcriptomic and proteomic level. Together, these studies suggest that MYC is central to the biology of IBC. Here, we analyzed data sets from patient samples and preclinical models to corroborate this hypothesis. Genomic and transcriptomic profiles were obtained using next-generation sequencing and Affymetrix GeneChip analysis on a series of 101 and 137 samples from patients with IBC. In addition, non-IBC (nIBC) control samples were included from our own repositories (N=252) as well as from publicly available data sets (i.e. TCGA and METABRIC). Finally, RNA-sequencing and peptide phosphorylation data from preclinical IBC and nIBC models, both with and without TGFβ treatment, were explored. Apart from TP53 and ERBB2, MYC is the 3rd most frequently mutated gene with single nucleotide variants, indels and amplifications found in 22% of 101 patients. Furthermore, MYC mutations are mutually exclusive with alterations in the NOTCH genes (i.e. NOTCH1, -2, -3, and -4 and CREBBP). At the gene expression level, a MYC activation score is elevated in IBC as compare to nIBC and correlates with a NOTCH activation signature. Genes overexpressed in IBC are enriched for various sets of MYC target genes and are associated with MYC amplifications in TCGA and METABRIC samples. In preclinical models, MYC target genes are particularly responsive to TGFβ treatment in IBC cells but not in nIBC cells and analysis of peptide phosphorylation patterns suggest this interaction may be regulated via PTK2B. The present data suggest that MYC could be an important driver of IBC biology, which corroborates with the recent observation that MYC is an important hub in the signal transduction network of SUM149 and -190 cells. Furthermore, our data reveal that MYC activation is linked to NOCTH and TGFβ signaling. In earlier studies it was demonstrated that lymphovascular tumor emboli in the Mary-X mouse model of IBC exhibit NOTCH3 addition with downstream MYC overexpression, indicating that NOTCH/MYC signaling could be crucial for metastatic progression in IBC. In this context, it should be noted that an allele associated with metastatic risk in IBC patients resides at the 8q24 locus that harbors the MYC gene. Citation Format: Charlotte Rypens, François Bertucci, Patrice Viens, John WM Martens, Marcel Smid, Carolien Schröder, Naoto T Ueno, Massimo Cristofanilli, Piet Dirix, Peter Vermeulen, Luc Dirix, Steven Van Laere. Inflammatory breast cancer exhibits amplification and transcriptional activation of MYC in conjunction with NOTCH and TGFβ signaling [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-03-03.

For none, one, or two polarities—How do POLO junctions fit best into industrial Si solar cells?

AbstractWe present a systematic study on the benefit of the implementation of poly‐Si on oxide (POLO) or related junctions into p‐type industrial Si solar cells as compared with the benchmark of Passivated Emitter and Rear Cell (PERC). We assess three aspects: (a) the simulated efficiency potential of representative structures with POLO junctions for none (=PERC+), one, and for two polarities; (b) possible lean process flows for their fabrication; and (c) experimental results on major building blocks. Synergistic efficiency gain analysis reveals that the exclusive suppression of the contact recombination for one polarity by POLO only yields moderate efficiency improvements between 0.23%abs and 0.41%abs as compared with PERC+ because of the remaining recombination paths. This problem is solved in a structure that includes POLO junctions for both polarities (POLO2), for whose realization we propose a lean process flow, and for which we experimentally demonstrate the most important building blocks. However, two experimental challenges—alignment tolerances and screen‐print metallization of p+ poly‐Si—are unsolved so far and reduced the efficiency of the “real” POLO2 cell as compared with an idealized scenario. As an intermediate step, we therefore work on a POLO IBC cell with POLO junctions for one polarity. It avoids the abovementioned challenges of the POLO2 structure, can be realized within a lean process flow, and has an efficiency benefit of 1.59%abs as compared with PERC—because not only contact recombination is suppressed but also the entire phosphorus emitter is replaced by an n+ POLO junction.