The Adipose Microenvironment Dysregulates the Mammary Myoepithelial Cells and Could Participate to the Progression of Breast Cancer

Abstract

Breast cancer is the most common cancer among women worldwide. Overweight and obesity are now recognized as established risk factors for this pathology in postmenopausal women. These conditions are also believed to be responsible for higher recurrence and mortality rates. Reciprocal interactions have been described between adipose and cancer cells. An adipose microenvironment favors a greater proliferation of cancer cells, their invasion and even resistance to anti-cancer treatments. In addition, the chronic low-grade inflammation observed in obese individuals is believed to amplify these processes. Among the cell types present in the breast, myoepithelial cells (MECs), located at the interface of the epithelial cells and the stroma, are considered “tumor suppressor” cells. During the transition from ductal carcinoma in situ to invasive cancer, disorganization or even the disappearance of MECs is observed, thereby enhancing the ability of the cancer cells to migrate. As the adipose microenvironment is now considered as a central actor in the progression of breast cancer, our objective was to evaluate if it could be involved in MEC functional modifications, leading to the transition of in situ to invasive carcinoma, particularly in obese patients. Through a co-culture model, we investigated the impact of human adipose stem cells from women of normal weight and obese women, differentiated or not into mature adipocytes, on the functionality of the MECs by measuring changes in viability, apoptosis, gene, and miRNA expressions. We found that adipose cells (precursors and differentiated adipocytes) could decrease the viability of the MECs, regardless of the original BMI. The adipose cells could also disrupt the expression of the genes involved in the maintenance of the extracellular matrix and to amplify the expression of leptin and inflammatory markers. miR-122-5p and miR-132-3p could also be considered as targets for adipose cells. The metabolite analyses revealed specific profiles that may be involved in the growth of neoplastic cells. All of these perturbations could thus be responsible for the loss of tumor suppressor status of MECs and promote the transition from in situ to invasive carcinoma.

Diverse breast adipose stromal cell biology in women at high risk for developing breast cancer

“…Leading theories point to chronic in ammation and the release of in ammatory cytokines from ASCs as a potential driver for breast cancer progression [12,13]. Most previous studies have only characterized the biology of ASCs from the abdomen [7,14].…”

Establishment of a New Cell Line of Canine Mammary Tumor CMT-1026

“…IHC results indicated that CMT-1026 was a basal epithelial cell line, and its positive expression of cytokeratin 5/6 (for basal epithelial cells) (55), α-SMA (for myoepithelial cells) (56), and P63 (for myoepithelial cells) (57) indicated that CMT-1026 was of epithelial origin. CMT cells frequently show myoepithelial proliferation leading to preinvasive carcinoma (58,59). CMT-1026 is also a well-established basal like subtype cell line (60).…”

Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

“…Experimental results showed that adipose cells led to a decrease in the viability of myoepithelial cells (MECs), which are known as tumor suppressor cells that block the transition from ductal carcinoma in situ to invasive carcinoma. Both leptin amplification and the disruption of genes involved in extracellular matrix maintenance were observed during this stage [51]. The effect of the adipokine leptin on normal mammary epithelial cells was investigated.…”