Breast Cancer Adipose Tissue Research Articles

Xonotlite Nanowire-Containing Bioactive Scaffolds for the Therapy of Defective Adipose Tissue in Breast Cancer.

Considering the challenge in the treatment of severe breast tumor patients, xonotlite nanowire-containing bioactive scaffolds (Fe3O4-CS-GelMA) were fabricated by the 3D-printing technique for the therapy of injured adipose tissue after surgery. Importantly, benefiting from the excellent magnetothermal performance of Fe3O4 microspheres, Fe3O4-CS-GelMA scaffolds could effectively kill tumor cells in vitro and suppress breast cancer in vivo under an alternating magnetic field, and the tumor did not recur in 2 weeks. In addition, attributed to the released bioactive inorganic ions, Fe3O4-CS-GelMA composite scaffolds could effectively promote the expression of adipogenesis-related genes and proteins of adipose-derived stem cells (ADSCs) via the PI3K-AKT signaling pathway in vitro. Furthermore, Fe3O4-CS-GelMA scaffolds with ADSCs could obviously stimulate the formation of adipose in vivo, compared with that of pure GelMA without inorganic components. Therefore, this study offers a promising strategy for the therapy of breast tumors after the surgical excision of breast carcinoma.

AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer

AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer

Breast adipose tissue macrophages (BATMs) have a stronger correlation with breast cancer survival than breast tumor stroma macrophages (BTSMs)

BackgroundAn abundance of tumor-associated macrophages has been shown to be an independent prognostic factor for a poor prognosis of human breast cancer (BC). Adipose tissue accounts for the largest proportion of the breast and has also been identified as an independent indicator of poor survival in BC. This study aims to elucidate if the influence of adipose tissue in BC might be mediated by macrophages. The roles of macrophages in the breast tumor-stroma (breast tumor stroma macrophages, BTSM) and macrophages in the surrounding adipose tissue (breast adipose tissue macrophages, BATM) were explored separately.MethodsTwo hundred ninety-eight BC tissue samples were analyzed immunohistochemically. The number of macrophages was detected by CD68+ staining. The quantity of BATMs and BTSMs was correlated to clinical and pathological parameters as well as to disease-free survival (DFS) and overall survival (OS).ResultsThe amounts of BATMs and BTSMs strongly correlated with each other (r = 0.5, p = 2.98E−15). The quantity of BTSMs, but not of BATMs, was significantly associated with the BC molecular subtype (p = 0.000011), and all triple-negative BC tumors contained high amounts of BTSMs. BATMs were negatively associated with DFS (p = 0.0332). Both BATMs (p = 0.000401) and BTSMs (p = 0.021) were negatively associated with OS in the Kaplan-Meier analysis, but only BATMs remained an independent factor in the multivariate Cox-regression analysis (HR = 4.464, p = 0.004). Combining prostaglandin E2 receptor 3 (EP3)-expression and the quantity of BATMs, a subgroup with an extremely poor prognosis could be identified (median OS 2.31 years in the “high BATMs/low EP3” subgroup compared to 11.42 years in the most favorable “low BATMs/high EP3” subgroup, p = 0.000002).ConclusionOur findings suggest that BTSMs and BATMs seem to be involved differently in BC. Breast adipose tissue might contribute to the aggressiveness of BC via BATMs, which were independently associated with BC survival. BATMs’ role and occurrence might be functionally dependent on EP3, as a combination of both factors was strongly associated with survival. Targeting BATMs—eventually in combination with targeting the EP3-pathway—might be promising for future therapies.

The Importance of Breast Adipose Tissue in Breast Cancer.

Adipose tissue is a complex endocrine organ, with a role in obesity and cancer. Adipose tissue is generally linked to excessive body fat, and it is well known that the female breast is rich in adipose tissue. Hence, one can wonder: what is the role of adipose tissue in the breast and why is it required? Adipose tissue as an organ consists of adipocytes, an extracellular matrix (ECM) and immune cells, with a significant role in the dynamics of breast changes throughout the life span of a female breast from puberty, pregnancy, lactation and involution. In this review, we will discuss the importance of breast adipose tissue in breast development and its involvement in breast changes happening during pregnancy, lactation and involution. We will focus on understanding the biology of breast adipose tissue, with an overview on its involvement in the various steps of breast cancer development and progression. The interaction between the breast adipose tissue surrounding cancer cells and vice-versa modifies the tumor microenvironment in favor of cancer. Understanding this mutual interaction and the role of breast adipose tissue in the tumor microenvironment could potentially raise the possibility of overcoming breast adipose tissue mediated resistance to therapies and finding novel candidates to target breast cancer.

Tumor-associated macrophages and crown-like structures in adipose tissue in breast cancer.

We aimed to evaluate macrophage infiltration and to identify the status of crown-like structures (CLSs) in mammary adipose tissue of human breast tissue in cases with and without breast cancer. Breast adipose tissue was obtained from reduction mammoplasty (N=56, Group 1), non-neoplastic breast tissue of breast cancer patients (N=84, Group 2), and breast cancer with adipose stroma (N=140, Group 3). Immunohistochemical staining of CD68 and CD163 was performed, and the infiltrating macrophages and CLSs within breast adipose tissue were evaluated. Group 3 had the largest number of CD68-positive (CD68+) and CD163-positive (CD163+) macrophages and CLSs within adipose tissue (P<0.001). Among Group 3, cases with high levels of CD68+ and CD163+ macrophages commonly had a higher histologic grade (P=0.016 and P=0.045), and cases with CD163+ CLSs were correlated with old age (P=0.042), estrogen receptor negativity (P=0.013), human epidermal growth factor receptor-2 positivity (P=0.043), and non-luminal A type (P=0.039). Upon univariate analysis, high levels of CD163+ macrophages were associated with shorter disease-free survival in node-negative breast cancer patients (P=0.033), and CD68+ CLSs were associated with shorter overall survival in node-positive breast cancer patients (P=0.015). CD68+ and/or CD163+ tumor-associated macrophage infiltration as well as CLSs are present in adipose tissue nearby the breast cancer lesion, and are associated with various clinicopathologic parameters of breast cancer.

P1-03-08: Adipose Tissue in Breast Cancer: Not an Idle Bystander but an Active Participant in Breast Cancer Progression.

Abstract Background: Adipose tissue is a dynamic organ that secretes a plethora of molecules called adipokines. In breast cancer we find a unique situation were genetically changed cells (the cancer cells) are in close contact with adipocytes. Moreover, obesity is a known negative prognostic marker for postmenopausal breast cancer patients. We hypothesize that adipocyte-derived factors influence breast cancer progression. Materials and methods: Adipose tissue was collected from breast cancer patients undergoing a mastectomy. After macroscopic removal of blood vessels and connective tissue, the adipose tissue was carefully cut into 2–3mm3 pieces and were incubated in specific adipose-tissue culture medium. After 24h, the medium was collected and the quality was checked by determining the concentration of total proteins, leptin, adiponectin, TNFalpha and triglycerides. This conditioned medium of adipose tissue (CM AT) was used for in vitro experimentation with MCF-7 breast cancer cells. Results: Effect of AT on morphology and aggregation: when MCF-7 cells are grown in a culture flask, they tend to form round compact islands. Under influence of CM AT, the islands form sharp edges, the cells in an island can be counted individually and they show scattering. Importantly, despite the major changes in cellular morphology, CM AT removal rescued the compact island formation of MCF-7 cells. In the slow aggregation assay, cells treated with CM AT (and a subtherapeutic concentration of a neutralizing E-cadherin antibody) lost the ability to form compact aggregates. Furthermore, MCF-7 spheroids placed inside adipose tissue showed massive reorganization into an irregularly shaped mass. Effect of AT on proliferation: starting from an equal number of cells and counting them every 2 days, it became clear that MCF-7 cells with CM AT had a higher rate of proliferation than MCF-7 cells in control medium. This stimulation of proliferation was confirmed by cell cycle analysis which revealed a doubling of cells in the G2/M phase, and western blot which showed an upregulation of cyclin A and cyclin E, both positive regulators of the cell cycle. Effect of AT on invasion: a 24h collagen type I invasion assay revealed invasive characteristics of MCF-7 cells treated with CM AT while MCF-7 cells in control conditions are round and non-invasive. In contrast, a transwell collagen test over 14 days was not able to show MCF-7 cells invading the collagen gel under influence of CM AT. However, the growth pattern of MCF-7 cells on the collagen gel was clearly disorganised when compared with the control situation. Conclusion: These findings suggest that adipose tissue-derived factors exert a dramatic selective force on patterning, invasion and growth of MCF-7 breast cancer cells. Unraveling the mechanism behind these observations may provide vital information regarding the link between obesity and poor prognosis in postmenopausal breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-03-08.