Fascin Expression Research Articles

Anti-Metastasis Fascin Inhibitors Decrease the Growth of Specific Subtypes of Cancers.

Fascin is an actin-bundling protein that is critical for filopodial formation and other cellular cytoskeletal structures. An elevated expression of fascin has been observed in tumor cells and is correlated with a shorter survival of cancer patients. Given its roles in tumor cell migration and invasion, we have developed small-molecule fascin inhibitors to prevent and delay tumor metastasis. Here we report the characterization of a new fascin inhibitor in mice. In addition to its inhibitory effects on tumor metastasis, we also report that fascin inhibitors can decrease the growth of specific subtypes of cancers, including epidermal growth factor receptor (EGFR)-high triple-negative breast cancer, and activated B-cell subtypes of diffuse large B-cell lymphoma. Hence, fascin inhibitors can be used to not only inhibit tumor metastasis, but also decrease the tumor growth of specific cancer types.

How does fascin promote cancer metastasis?

Fascin is an F-actin-bundling protein that cross-links individual actin filaments into straight and stiff bundles. Fascin overexpression in cancer is strongly associated with poor prognosis and metastatic progression across different cancer types. It is well established that fascin plays a causative role in promoting metastatic progression. We will review the recent progress in our understanding of mechanisms underlying fascin-mediated cancer metastasis. This review will cover the biochemical basis for fascin-bundling activity, the mechanisms by which cancer cells upregulate fascin expression and the mechanism underlying fascin-mediated cancer cell migration, invasion, and metastatic colonization. We propose that fascin has broad roles in both metastatic dissemination and metastatic colonization. Understanding these mechanisms will be crucial to the development of anti-metastasis therapeutics targeting fascin.

Roles of Fascin mRNA expression in colorectal cancer: Meta-analysis and bioinformatics analysis.

Fascin (encoded by FSCN1) is a globular actin cross-linking protein that is required for the formation of actin-based cell surface processes, which are critical for cell migration and cell-matrix adhesion. In the present study, a systematic meta-analysis and bioinformatics analysis was used to identify clinicopathological or prognostic parameters in patients with colorectal cancer. A total of 17 articles were included in the present study obtained from PubMed, Web of Science, Wanfang data, SinoMed and CNKI databases. Odd ratios (ORs) and the corresponding 95% confidence intervals (CIs) were used to estimate the prognostic significance of Fascin expression in patients with colorectal cancer, and the association between Fascin expression and clinicopathological factors. There was a significant correlation between high Fascin expression and poor overall survival rates in patients with colorectal cancer (OR=0.48; 95% CI, 0.38-0.60; P<0.000001). The meta-analysis showed that the expression of Fascin was significantly higher in colorectal cancer tissue compared with the normal mucosa (OR=0.13; 95% CI, 0.10-0.16; P<0.000001) and adenoma (OR=0.23; 95% CI, 0.15-0.34; P<0.000001). Fascin expression was also associated with depth of invasion (OR=0.31; 95% CI, 0.19-0.50; P<0.000001), lymph node metastasis (OR=3.07; 95% CI, 1.72-5.46; P=0.0001), Dukes stage (OR=0.14; 95% CI, 0.04-0.46; P=0.001), Tumor-Node-Metastasis stage (OR=0.38; 95% CI, 0.21-0.71; P=0.003) and dedifferentiation (OR=0.42; 95% CI, 0.19-0.94; P=0.04). According to the bioinformatics analyses, FSCN1 mRNA expression levels were higher in colorectal cancer and adenoma tissues compared with the normal tissues (P<0.05). According to TCGA, FSCN1 mRNA expression was associated with a less favorable prognosis in patients with colorectal cancer as an independent factor (P<0.05), and positively correlated with depth of invasion, microsatellite instability and low serum carcinoembryonic antigen levels in colorectal cancer. Taken together, the results of the present study suggested that Fascin expression is a potential marker of tumorigenesis, aggressiveness and poor prognosis in patients with colorectal cancer.

FSCN1 as prognostic marker in borderline tumors of the ovary.

e18061 Background: Risk factors for invasive recurrence of borderline tumours (BOT) of the ovary are needed. The actin-bundling protein Fascin-1 (FSCN1) is involved in alteration of adhesion and cell motility and has been associated with invasion and metastasis in different cancers. Methods: We studied a retrospective cohort of 124 bordeline tumors of the ovary (BOT) with validated diagnosis by an independent pathologist for expression of FSCN1 as potential prognostic biomarker. Results: We found strong expression of the actin-bundling protein FSCN1 in 62 of these tumors. FSCN1 positive patients were slightly younger (46.9±2.2 vs. 53.3±2.3 years, P = 0.049). Expression of FSCN1 was more frequently detected in BOT with serous compared to mucinous histotype (58/78 [74.4%] vs. 3/41 [7.3%], p &lt; 0.001), and in cases with micropapillary pattern (25/28 [89.3%] vs. 38/98 [38.8%], P &lt; 0.001). In addition, a non significant trend was observed for more frequent expression of FSCN1 among cases with implants (8/10 [80.0%] vs. 55/116 [47.4%], P = 0.095). When we compared progression free survival of the patients we found numerical lower but not statistically significant PFS rates of 90.5±6.4% vs. 94.4±5.4% for 10 years, and 81.4±10.3% vs. 94.4±5.4% for 15 years, in BOT with FSCN1 expression compared to those tumors negative for FSCN1, respectively. Conclusions: Our analysis suggests an association of FSCN1 expression in BOT with micropapillary pattern and implants, which have been linked to inferior prognosis. Cases with FSCN1 expression in our cohort displayed numerical lower PFS rates prompting further studies of this marker.

BP-1-102 and silencing of Fascin-1 by RNA interference inhibits the proliferation of mouse pituitary adenoma AtT20 cells via the signal transducer and activator of transcription 3/fascin-1 pathway

Introduction The expression levels of signal transducer and activator of transcription 3 (STAT3) protein and Fascin-1 were inhibited using the STAT3 inhibitor BP-1-102 and RNA interference, respectively, to investigate the expression of AtT20 in mouse pituitary cells. The proliferative capacity and related molecular mechanisms of pituitary tumor cells were then analyzed. Methods Mouse AtT20 pituitary adenoma cells were divided into a control group (Pa group), a STAT3 inhibitor vehicle group (PA + DMSO group), a STAT3 inhibitor group (PA + BP-1-102 group), a Fascin-1 negative control group (PA + neg-siRNA group) and a Fascin-1 silenced group (PA + Fascin-siRNA group). The related protein expression and cell proliferation of the five groups were measured using immunofluorescence, Western blot and real-time RT-PCR, whereas their apoptosis and cell cycle were evaluated using CCK-8 and flow cytometry. Results Proliferation of AtT20 cells is inhibited with BP-1-102 enhanced apoptosis, at the same time reduced the expression of Fascin-1 and N-cadherin, and increased the expression of E-cadherin. After inhibiting Fascin-1, the expression of STAT3 decreased, the expression of N-cadherin decreased and the expression of E-cadherin increased. Conclusions BP-1-102 is a novel drug with a great potential in pituitary tumors. Given their important roles in the growth of pituitary adenomas, STAT3 and Fascin-1 can be used as new treatment targets.

Fascin Activates β-Catenin Signaling and Promotes Breast Cancer Stem Cell Function Mainly Through Focal Adhesion Kinase (FAK): Relation With Disease Progression.

Cancer stem cells (CSCs), a rare population of tumor cells with high self-renewability potential, have gained increasing attention due to their contribution to chemoresistance and metastasis. We have previously demonstrated a critical role for the actin-bundling protein (fascin) in mediating breast cancer chemoresistance through activation of focal adhesion kinase (FAK). The latter is known to trigger the β-catenin signaling pathway. Whether fascin activation of FAK would ultimately trigger β-catenin signaling pathway has not been elucidated. Here, we assessed the effect of fascin manipulation in breast cancer cells on triggering β-catenin downstream targets and its dependence on FAK. Gain and loss of fascin expression showed its direct effect on the constitutive expression of β-catenin downstream targets and enhancement of self-renewability. In addition, fascin was essential for glycogen synthase kinase 3β inhibitor–mediated inducible expression and function of the β-catenin downstream targets. Importantly, fascin-mediated constitutive and inducible expression of β-catenin downstream targets, as well as its subsequent effect on CSC function, was at least partially FAK dependent. To assess the clinical relevance of the in vitro findings, we evaluated the consequence of fascin, FAK, and β-catenin downstream target coexpression on the outcome of breast cancer patient survival. Patients with coexpression of fascinhigh and FAKhigh or high β-catenin downstream targets showed the worst survival outcome, whereas in fascinlow, patient coexpression of FAKhigh or high β-catenin targets had less significant effect on the survival. Altogether, our data demonstrated the critical role of fascin-mediated β-catenin activation and its dependence on intact FAK signaling to promote breast CSC function. These findings suggest that targeting of fascin–FAK-β-catenin axis may provide a novel therapeutic approach for eradication of breast cancer from the root.

MiR-200b/c family inhibits renal fibrosis through modulating epithelial-to-mesenchymal transition via targeting fascin-1/CD44 axis

BackgroundRenal fibrosis is the characteristic of all kinds of chronic kidney diseases (CKDs). Fascin-1 plays an important role in tumor development, but the roles of fascin-1 in renal fibrosis have not been studied. Here, we explored the role of fascin-1 in renal fibrosis and the potential mechanisms. MethodsKidney unilateral ureteral obstruction (UUO) mouse model was used as an in vivo model, and proximal tubule epithelial cell lines treated with TGF-β1 were used as in vitro model of renal fibrosis. Cell transfection was performed to manipulate the expression of miR-200b/c, fascin-1 and CD44. Western blotting, qRT-PCR, immunohistochemistry or immunofluorescence assays were used to measure levels of miR-200b/c, fascin-1, CD44, and fibrosis and EMT-related markers. H&E and Masson stainings were used to examine the degree of injury and fibrosis in kidneys. Dual luciferase assay was used to examine the interaction between miR-200b/c family and fascin-1. ResultsFascin-1 and CD44 levels were both significantly up-regulated while miR-200b/c family was reduced in models of renal fibrosis. Furthermore, overexpression of miR-200b/c family and inhibition of fascin-1 or CD44 ameliorated renal fibrosis through suppressing EMT process. Mechanistically, miR-200b/c family directly and negatively regulated the expression of fascin-1. Overexpression of fascin-1 could reverse the effects of miR-200b/c family on renal fibrosis, and fascin-1 regulated renal fibrosis by activating CD44. ConclusionOur study is the first to show that fascin-1 plays a critical role in renal fibrosis. MiR-200b/c family could inhibit renal fibrosis through modulating EMT process by directly targeting fascin-1/CD44 axis.

New role of the antidepressant imipramine as a Fascin1 inhibitor in colorectal cancer cells

Serrated adenocarcinoma (SAC) is more invasive, has worse outcomes than conventional colorectal carcinoma (CRC), and is characterized by frequent resistance to anti-epidermal growth factor receptor (EGFR) and overexpression of fascin1, a key protein in actin bundling that plays a causative role in tumor invasion and is overexpressed in different cancer types with poor prognosis. In silico screening of 9591 compounds, including 2037 approved by the Food and Drug Administration (FDA), was performed, and selected compounds were analyzed for their fascin1 binding affinity by differential scanning fluorescence. The results were compared with migrastatin as a typical fascin1 inhibitor. In silico screening and differential scanning fluorescence yielded the FDA-approved antidepressant imipramine as the most evident potential fascin1 blocker. Biophysical and different in vitro actin-bundling assays confirm this activity. Subsequent assays investigating lamellipodia formation and migration and invasion of colorectal cancer cells in vitro using 3D human tissue demonstrated anti-fascin1 and anti-invasive activities of imipramine. Furthermore, expression profiling suggests the activity of imipramine on the actin cytoskeleton. Moreover, in vivo studies using a zebrafish invasion model showed that imipramine is tolerated, its anti-invasive and antimetastatic activities are dose-dependent, and it is associated with both constitutive and induced fascin1 expression. This is the first study that demonstrates an antitumoral role of imipramine as a fascin1 inhibitor and constitutes a foundation for a molecular targeted therapy for SAC and other fascin1-overexpressing tumors.

Novel anti-invasive properties of a Fascin1 inhibitor on colorectal cancer cells.

Tumor invasion and metastasis involve processes in which actin cytoskeleton rearrangement induced by Fascin1 plays a crucial role. Indeed, Fascin1 has been found overexpressed in tumors with worse prognosis. Migrastatin and its analogues target Fascin1 and inhibit its activity. However, there is need for novel and smaller Fascin1 inhibitors. The aim of this study was to assess the effect of compound G2 in colorectal cancer cell lines and compare it to migrastatin in in vitro and in vivo assays. Molecular modeling, actin-bundling, cell viability, inmunofluorescence, migration, and invasion assays were carried out in order to test anti-migratory and anti-invasive properties of compound G2. In addition, the in vivo effect of compound G2 was evaluated in a zebrafish model of invasion. HCT-116 cells exhibited the highest Fascin1 expression from eight tested colorectal cancer cell lines. Compound G2 showed important inhibitory effects on actin bundling, filopodia formation, migration, and invasion in different cell lines. Moreover, compound G2 treatment resulted in significant reduction of invasion of DLD-1 overexpressing Fascin1 and HCT-116 in zebrafish larvae xenografts; this effect being less evident in Fascin1 known-down HCT-116 cells. This study proves, for the first time, the in vitro and in vivo anti-tumoral activity of compound G2 on colorectal cancer cells and guides to design improved compound G2-based Fascin1 inhibitors. KEY MESSAGES: • Fascin is crucial for tumor invasion and metastasis and is overexpressed in bad prognostic tumors. • Several adverse tumors overexpress Fascin1 and lack targeted therapy. • Anti-fascin G2 is for the first time evaluated in colorectal carcinoma and compared with migrastatin. • Filopodia formation, migration activity, and invasion in vitro and in vivo assays were performed. • G2 blocks actin structures, migration, and invasion of colorectal cancer cells as fascin-dependent.

The therapeutic effects of blocking IGF-R1 on mice model of skin cancer

Background and objectives The incidence of skin cancer has raised in the last few years. One of the important growth factors found in the skin layers is insulin-like growth factor (IGF)-1. It is directly linked with many cancers in different organs. Therefore, we aimed to explore the therapeutic effects of blocking IGF-1 receptor (IGF-R1) pathway by PQ401 in skin cancer as well as studying its effect on tumor invasion markers. Materials and methods We experimentally induced skin cancer in mice by the application of 7,12-dimethylbenz (a) anthracene. Skin samples were removed for determination of gen and protein expression of IGF-1, IGF-R1, glypican-3, MMP9, syndecan-1 and fascin-1 by Western blot and PCR. Moreover, skin sections were stained with hematoxylin/eosin and Mallory. Results Treatment with PQ401 blocked the expression of IGF-R1 in the skin, which is associated with reduction in the skin cancer-induced tumors and scratches. In addition, PQ401 ameliorated skin cancer induced formation of epidermal atypia and hyperplasia. PQ401 reduced both gene and protein expression of the tumor invasion markers, MMP9, syndecan-1 and fascin-1, without affecting gene and protein expression of glypican-3 and IGF-1 in skin cancer group. Conclusion Blocking IGF-R1 has therapeutic effects against experimental skin cancer induced in mice. In addition, blocking IGF = R1 attenuated skin cancer-induced activation of tumor invasion markers. Key points IGF-1/IGF-R1is highly expressed in different cancers as skin cancer. Blocking IGF-R1 production ameliorated skin cancer. Blocking IGF-R1 attenuated skin cancer-induced activation of tumor invasion markers.

Effects of Galectin-1 on Biological Behavior in Cervical Cancer.

Background: We previously revealed that the expression of galectin-1 (LGALS1) was significantly reduced after neoadjuvant chemotherapy treatment in cervical cancer patients. The objective of this study is to investigate the effects of LGALS1 expression on biological behaviors of cervical cancer cells.Methods: Immunohistochemistry and immunocytochemistry were performed to detect the expression of LGALS1 in cervical cancer tissues and cells (SiHa and C33A). Western blot analysis was performed to evaluate the efficacy of lentivirus-mediated upregulation or downregulation of LGALS1 in cervical cancer cells. Cell viability and proliferation were detected by CCK-8 and BrdU assays, respectively. Annexin V-FITC/PI apoptosis detection kit was employed to measure the apoptosis of cervical cancer cells. Transwell invasion and migration assays were also conducted to explore the invasive and migratory capabilities of cervical cancer cells. The expression of apoptosis- (Bcl-2 and Bax), invasion- (MMP-2 and MMP-9), and migration-related (Fascin and Ezrin) proteins, were detected by Western blot analysis. Xenograft mouse model of cervical cancer was generated to explore whether LGALS1 overexpression could promote tumor growth in vivo.Results: LGALS1 was overexpressed in cervical cancer tissues and cell lines compared to that in normal cervical tissues and epithelium cells. Upregulation of LGALS1 significantly promoted the cell proliferation, inhibited cell apoptosis, and enhanced the migratory and invasive abilities of both SiHa and C33A cells, whereas downregulation of LGALS1 led to the opposite results. The level of Bcl-2, MMP-2, MMP-9, Fascin, and Erzin expression was significantly upregulated in cervical cancer cells with LGALS1 overexpression, while converse results were obtained in LGALS1 knockdown cancer cells. In vivo study also showed that LGALS1 overexpression facilitated tumor growth of cervical cancer cells.Conclusion: Overexpression of LGALS1 significantly promoted and enhanced the aggressive features of cervical cancer both in vitro and in vivo, which may be associated with high expression of Bcl-2, MMP-2, MMP-9, Fascin, and Erzin proteins.

Inhibition of the proliferation, migration, and invasion of human breast cancer cells by leucine aminopeptidase 3 inhibitors derived from natural marine products.

Leucine aminopeptidase 3 is involved in the progression and metastasis of several cancers. This study aimed to screen anti-tumor lead compounds targeting leucine aminopeptidase 3. The compounds' suppression effect on enzyme activity and anti-tumor activity were evaluated through a series of assays. Leucine aminopeptidase 3 overexpression K562 cells were used as an enzyme source to screen 43 natural marine compounds. Compounds 5 and 6 exhibited high suppression effect on leucine aminopeptidase 3 activity. Cell activity tests indicated that both compounds have an anti-proliferative effect on triple-negative breast cancer cells. Wound healing assay and transwell invasion assay showed that both compounds could inhibit the migration and invasion of breast cancer cells. Immunoblot analysis exhibited that both compounds could downregulate the expression of metastasis-related proteins fascin and matrix metalloproteinase-2/9. A molecular dynamic simulation process was applied to discover the key features of compounds 5 and 6 in binding to leucine aminopeptidase 3 active site. This study described the anti-tumor effects of two leucine aminopeptidase 3 small molecule inhibitors. Taken together, compounds 5 and 6 could be used as anti-tumor lead compounds targeting leucine aminopeptidase 3.

Features of fascin expression in the small intestine of rats exposed to processed Eucheuma seaweed

This study focuses on the assessment of fascin expression in the small intestinal tissue of rats orally administered a food additive E407a (processed Eucheuma seaweed), which is widely used to improve the texture of food products. The issue of its safety is under debate nowadays. Small intestinal expression of fascin, an actin-bundling cytoskeletal protein involved in the formation of filopodia and microspikes, was evaluated immunohistochemically in 9 rats exposed to 140 mg of E407a per kg of weight daily during two weeks and 8 control animals. Fascin was found to be upregulated both in the lamina propria and epithelia of the small intestine in rats administered processed Eucheuma seaweed compared with the control group. Thus, oral consumption of E407a is associated with overexpression of fascin in the small intestine of rats.

RETRACTED: Silencing lncRNAs PVT1 Upregulates miR-145 and Confers Inhibitory Effects on Viability, Invasion, and Migration in EC

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is correlated to various malignant tumors. Consequently, we explored effects of lncRNA PVT1 on esophageal carcinoma (EC) targeting microRNA-145 (miR-145). EC tissues, adjacent normal tissues, and EC-related cell lines were collected and cultured. Expression of lncRNA PVT1, miR-145, fascin-1 (FSCN1), and related genes with intervening expression of PVT1 and miR-145 was determined. Bioinformatic website, dual-luciferase reporter assay, and RNA immunoprecipitation (RIP) were carried to verify target relationship among lncRNA PVT1, FSCN1, and miR-145. Scratch test, Transwell assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and flow cytometry were performed for detection of migration, invasion, viability, and apoptosis of transfected cells, respectively. Finally, tumor formation in nude mice was measured. After database analysis, lncRNA PVT1, miR-145, and FSCN1 were selected for study. lncRNA PVT1 and FSCN1 can bind to miR-145. After overexpressing miR-145 or inhibiting lncRNA PVT1, EC cell viability, migration, and invasion were inhibited, while volume and weight of tumor formation in nude mice decreased. Expression of lncRNA PVT1, FSCN1, Bcl-2, CD147, VEGFR2, and MTA1 decreased and expression of miR-145 and Bax increased. Silencing lncRNA PVT1 can upregulate miR-145, which is a tumor suppressor in EC via knockdown of FSCN1. Thus, we might provide a potential theoretical basis for EC treatment.

Abstract C053: NP-G2-044, a novel fascin inhibitor, blocks tumor metastasis and increases antitumor immune response

Abstract Filopodia are finger-like plasma membrane protrusions that are formed upon remodeling of the actin cytoskeleton beneath the plasma membrane. Fascin protein is the main actin-bundling protein in filopodia and invadopodia which are fundamental to cell shape and motility events. Human fascin expression is low or absent in normal adult epithelial cells but highly expressed in metastatic tumors and in antigen-presenting dendritic cells within the tumor microenvironment. Elevated levels of fascin are correlated with poor prognosis and short survival due to aggressive phenotypes with increased lymph node and distant metastases. Mouse genetic studies demonstrate that deletion of fascin gene delays tumor development, slows tumor growth, reduces metastatic colonization, and increases overall survival. These mouse genetic studies provide strong evidence for fascin’s role in tumor initiation, tumor progression and tumor metastasis, making it an attractive target for drug development. Chemical libraries were screened to identify small-molecule compounds that specifically inhibit the biochemical function of fascin to bundle actin filaments. The inhibitors were optimized to produce the lead compound, NP-G2-044. Preclinical studies showed that fascin inhibitors increase the overall survival of tumor-bearing mice and reinvigorate anti-tumor immune response in syngeneic mouse models of breast, lung, pancreatic and prostate tumors. Fascin protein levels are increased in conventional dendritic cells (cDCs) in the immunosuppressive tumor microenvironment. The number of intra-tumoral activated cDCs is increased following fascin inhibitor treatment. Moreover, together with anti-PD-1 antibody, fascin inhibition markedly increases the number of Ki67+ proliferating and Granzyme-B+ activated CD8+ killer T-cells in tumor tissue. These data demonstrate that fascin inhibitors simultaneously act on tumor cells to block tumor metastasis and on intratumoral DCs to reinvigorate anti-tumor immune response. We are currently conducting a first-in-human phase 1 trial of NP-G2-044 in patients with advanced or metastatic solid tumor malignancies. Citation Format: Vincent Chung, Frank Tsai, Komal Jhaveri, Yufeng Wang, Daniel D Von Hoff, Edward G Garmey, J. Jillian Zhang, Xin-Yun Huang. NP-G2-044, a novel fascin inhibitor, blocks tumor metastasis and increases antitumor immune response [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C053. doi:10.1158/1535-7163.TARG-19-C053

Actin-Bundling Proteins (Actinin-4 and Fascin-1) are Involved in the Development of Pancreatic Intraepithelial Neoplasia (PanIN)

Fascin-1 and actinin-4 are involved in key processes of tumor cell adhesion, migration and metastasis. Actinin-4 plays an important role in promotion of cell proliferation, whereas fascin-1 regulates cellular motility. Its over-expression leads to the loss of cell adhesion and metastasis. The aim of our study was to assess fascin-1 and actinin-4 expression in normal pancreatic ducts and in pancreatic intraepithelial neoplasia (PanIN) - precursor lesion of pancreatic ductal adenocarcinoma (PDAC). The study involved 70 patients treated surgically due to PDAC, cysts and pancreatitis, who had also been diagnosed with pancreatic intraepithelial neoplasia. Fascin-1 and actinin-4 expressions were evaluated using the immunohistochemistry method. A statistically significant relationship was observed between the expression of fascin-1 and actinin-4 (cytoplasmic) and patients' age (P=0.01, P=0.002, respectively). The expression of fascin-1 and actinin-4 was associated with the diagnosis (P<0.001,P=0.04, respectively). Statistical analysis revealed correlations of fascin-1 and actinin-4 expressions with the presence and grade of PanIN (P < 0.001, P=0.002, respectively). The expression of these proteins was observed in each degree of PanIN and increased with the pancreatic intraepithelial neoplasia progression. The expression of fascin-1 and actinin-4 is connected with the degree of PanIN advancement and depends on the type of the primary disease. Overexpression of these proteins may be linked to cytological and architectural abnormalities observed in advanced PanIN. Elevated expression of fascin-1 and actinin-4 indicates the role of these proteins in the progression from PanIN to PDAC.

Assessment of Fascin by immunohistochemistry in colorectal carcinoma

Background: The increased incidence of colon cancer may be attributed to an increase in the awareness of the disease, accessible screening modalities through widespread availability of preventive health check-ups & affordable newer imaging techniques. One of the essential components of clinical management of colon cancer is histopathological diagnosis and the role of Fascin-1 expression in colon cancers remains unexplored. This study was carried out to evaluate the fascin-1 expression in colon cancer specimens. Methods: This retrospective study was carried out on 60 paraffin blocks of colorectal carcinoma specimens received for a period of four years. IHC for Fascin was done on the sections along with controls. Clinical data regarding the participant’s demographics and medical history were captured from the hospital medical records. Gross findings were recorded from the blocks. Blocks with section containing normal epithelium and tumour were chosen for immunohistochemistry. Results: There was a significant association between pT1/pT2 staging and grade 0 fascin expression (80%) compared to those with pT3/pT4 staging (50%) (p<0.05). Similarly, grade 1 had strong positive correlation with fascin expression (70%) compared to other grades of the tumor (p<0.05). Conclusion: Presence of fascin expression significantly indicates the metastatic potential of colon carcinomas. Further research is required to delineate the mechanism of fascin expression at the cellular level in determining the prognosis of colon cancers.

P10.01 Anti-migration and anti-invasion effects of curcumin via suppression of fascin expression in glioblastoma cells

Abstract BACKGROUND The natural compound Curcumin was known to inhibit migration and invasion of glioblastoma (GBM) cells. Fascin, a kind of actin-binding proteins, is correlated with migration and invasion of GBM cells. The purpose of this study was to investigate anti-migration and anti-invasion effects of Curcumin via suppression of fascin expression in GBM cells. MATERIAL AND METHODS U87 cell line was used as an experimental model of GBM. Fascin was quantified by Western blot analysis. And, the signal transducer and activator of transcription 3 (STAT3), known to play an important role in migration and invasion of tumor cells, were analyzed by sandwich-ELISA. Migration and invasion capacities were assessed by attachment, migration and invasion assays. Cellular morphology was demonstrated by immunofluorescence. RESULTS At various concentrations of curcumin and exposure times, fascin expression decreased. After temporarily exposure to 10μM/L Curcumin during 6 hours as less invasive concentration and time, fascin expression temporarily decreased at 12 hours (18.4%, p=0.024), and since then recovered. And, the change of phosphrylated STAT3 level also reflected the temporarily decreased pattern of fascin expression at 12 hours (19.7%, p=0.010). Attachment, migration, and invasion capacities consistently decreased at 6, 12, and 24 hours. And, immunofluorescence showed the change of shape and the reduction of filopodia formation in cells. CONCLUSION Curcumin is likely to suppress the fascin expression in GBM cells, and this might be a possible mechanism for anti-migration and anti-invasion effects of Curcumin via inhibition of STAT3 phosphorylation.

Recombinant porcine NK-lysin inhibits the invasion of hepatocellular carcinoma cells in vitro

The therapeutics having ability to target cancer cells specifically and exhibit nominal cytopathic effect on normal healthy cells are highly significant for cancer therapeutic applications. Recombinant porcine natural killer lysin (rpNK-lysin) has proven cationic anti-bacterial and anti-tumor peptide. Herein, we report its anti-invasion and anti-metastasis effects on hepatocellular carcinoma (HCC) cells in vitro. We first investigate the maximum non-toxic concentration (MNTC) of rpNK-lysin for the normal hepato cells (L-02). Using MNTC rpNK-lysin, we explore anti-proliferative, anti-adhesive, anti-invasive and anti-metastatic effect of rpNK-lysin on three different HCC cells lines (SMMC-7721, 97-H and HepG2) through MTT, wound-healing, adhesion and invasion assay along with mRNA and protein expression. The results reveal that rpNK-lysin has potential to specifically inhibit HCC cells growth in a dose and time-dependent manner with a little cytopathic effect on the L-02 cells, effectively reduce migration, adhesion and invasion ability of HCC cells. rpNK-lysin significantly reduce Fascin1 expression, which subsequently decrease β-catenin expression and metaloproteinases (MMP-2 and MMP9). This study suggest that MNTC rpNK-lysin has an anti-invasion and anti-metastasis effect on HCC cells in vitro through inhibition of Fascin 1 expression which regulates Wnt/β-catenin signaling pathway by inducing β-catenin degradation and subsequently results in suppression of MMP-2 and MMP9 expression.

Spinal versus intracranial meningioma: Expression of E-cadherin and Fascin with relation to clinicopathological features.

E-cadherin and Fascin are adhesive proteins that are expressed in many tumors. It was supposed that loss of expression of these proteins is associated with increased aggressiveness of the tumor. Whether spinal and intracranial meningiomas express adhesion proteins in different rates is not yet known. We aimed to investigate the expression of E-cadherin and Fascin in a large number of meningioma specimens and determine if clinical and prognostic significance existsMETHODS: One hundred and thirty-four spinal and intracranial meningioma samples were collected. Manual TMA blocks were constructed and immunohistochemistry for E-cadherin and Fascin was done. Focal or diffuse staining was considered positive. Intracranial meningioma occurred in significantly younger age than spinal ones. Most of spinal meningiomas were of transitional histology. E-cadherin was expressed in 38.8% of cases. Spinal meningiomas showed statistically significant negative expression of E-cadherin than intracranial tumors. All atypical meningiomas showed negative E-cadherin expression. Fascin was expressed in 9% of cases with significant expression in atypical cases. Aggressive behavior of meningioma could be explained in part by loss of E-cadherin and overexpression of Fascin especially in spinal meningiomas. Further studies are suggested to explore the biological aspects of spinal and intracranial meningiomas for constructing tailored targeted therapies.