The Contribution of Different Adipose Tissue Depots in Obesity to Epithelial-mesenchymal Transition of Colorectal Cancer Cells.

Obesity is a progressive chronic disease, characterized by the release of pro-inflammatory mediators by the white adipose tissue. These mediators can promote the malignancy of tumor cells. Colorectal cancer ranks as the second leading cause of cancer-related deaths due to its high mortality rate. A key factor in its lethality is its ability to spread to other tissues, facilitated by the process of epithelial-mesenchymal transition (EMT), when cells loss epitelial characteristics, gaining mesenchymal markers and improving motility. OBJECTIVE: To investigate whether the secretome of adipose tissue deposits from patients with obesity could promote EMT in HT29 human colon adenocarcinoma cells, increasing their malignancy. METHODS: The research received approval from HUPE-UERJ ethics committee (CAAE:5602121.2.0000.5259). HT29 cells were treated with adipose tissue (AT) secretome obtained from subcutaneous (SAT), omental (OAT) or mesenteric (MAT) AT from patients with obesity undergoing bariatric surgery as described (Ramos-Andrade et al, 2020) doi.org/10.1530/ERC-19-0507). Cells were cultured in McCoy’s medium (10% SFB) supplemented or not with SAT, OAT or MAT. Cell viability and proliferation were assessed by MTT assay (48hrs), and counting of DAPI+ cells, respectively. Cell morphology was evaluated by optical microscopy and the expression of epithelial (Claudin-3) and mesenchymal (α-SMA) markers quantified by Western Blott. RESULTS: The secretome from any obese AT depots did not affect cell viability. However, MATS and OATS increased cell proliferation, and reduced epithelial cells aggregation. SATS reduced Claudin-3 expression and MATS increased α-SMA in HT29 cells compared to control. CONCLUSION:  The secretome of visceral AT improve malignant characteristics in HT29 cells during obesity, driving cells towards EMT. Financial support: CNPq, DECIT-MS, FAPERJ.