In vitro study of the interaction between adipose tissue and cancer cells, using the precision-cut adipose tissue slices method

Details

Supervisors

Debier, Cathy ; Pirard, Laura

Faculty

Faculté des bioingénieurs

Degree label

Master [120] : bioingénieur en chimie et bioindustries, à finalité spécialisée

Abstract

Besides its energy storage function, adipose tissue is considered as a functional endocrine and paracrine organ contributing to the maintenance of body homeostasis. The metabolism of adipose tissue can be disrupted by diseases such as cancer. In turn, the tumor microenvironment is crucial for cancer growth and invasion particularly in cancers located near an adipose tissue depot such as breast, ovarian, colon, prostate, skin, and pancreatic cancers. Since adipocytes are the main components of breast tissue, gaining a better understanding of the interaction between adipose tissue and tumors is an essential issue in breast cancer research. Cancer cells induce adipose tissue dysfunction transforming adipocytes into cancer-associated adipocytes. In turn, those adipocytes release lipids and adipokines contributing to cancer progression. However, detailed mechanisms remain unclear. This master thesis aimed at developing an in vitro method to study the interaction between adipose tissue and cancer cells. For the study of adipose tissue, pig precision-cut adipose tissue slices form a tissue culture method mimicking the structure and the function of the whole organ. Conditioned-medium and co-culture experiments have been set up to evaluate the impact of cancer cells on the lipolysis of pig precision-cut adipose tissue slices. MCF-7 and Hs578T breast cancer cell lines were used, and the phenomenon of acidosis was investigated with acidosis-adapted cancer cells and spheroids (FaDu and HCT116 cell lines). Gene expression analysis on adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL), was performed to deeper investigate interacting mechanisms between adipose tissue and cancer cells. Unexpected results were obtained: the lipolysis of pig precision-cut adipose tissue slices was decreased both in conditioned-medium experiments from cancer cells and in co-culture with cancer cells. Several hypotheses that could explain those results were discussed. Notably, the presence of fetal bovine serum in the culture medium, the time to generate the conditioned-medium, and the cross-species model were discussed. Concerning gene expression analysis, the expression of ATGL in precision-cut adipose tissue slices was decreased when they were cultured in conditioned-medium from breast cancer cells in presence of albumin and isoproterenol. Further investigations that vary discussed-parameters should provide explanations to our unexpected results and numerous questions are yet to be addressed to understand the mechanism of adipocytes-tumors crosstalk.