Le rôle de l'acétate dans le communication entre les adipocytes et les cellules tumorales

Details

Supervisors

Van Hul, Matthias

Degree label

Master [120] en sciences biomédicales, à finalité approfondie

Abstract

Breast cancer is the most common cancer in women worldwide and has the highest mortality rates. It is associated with various risk factors including obesity. Communication between tumor and adipocyte cells in the breast promotes cancer progression, notably through the exchange of nutrients. Indeed, cancer cells induce lipolysis within the adipocytes and capture the released free fatty acids. In addition, the microbiota ferments dietary fibers into short-chain fatty acids, including acetate, which can act on adipocytes by binding to the GPR43 receptor and inhibit lipolysis. The aim of this thesis is to verify in vitro whether the lipolysis induced in adipocytes by tumor cells can be inhibited by acetate through its binding to the GPR43 receptor. The main objective is to determine whether acetate could indirectly inhibit tumor progression. The role of acetate on adipocyte differentiation is evaluated. It turns out that this molecule does not influence the differentiation of our cell clones. Following an examination of different cancer cell lines, the 4T1 line was identified as the one that induces the most important lipolysis in mature adipocytes. Acetate fails to inhibit this induced lipolysis in adipose cells. Subsequently, viability and proliferation studies in tumor cells revealed that conditioning of the culture medium by adipocytes increases cell density but that acetate does not revert this effect. Then, analyses of lipid metabolism in tumor cells are performed to define the impact of free fatty acids coming from adipocyte lipolysis in the communication between adipocytes and tumor cells. Later, an inhibitor of the adipose triglyceride lipase is used for its ability to prevent lipolysis within adipocytes thus study the indirect effect of this inhibition on cancer cell viability. In conclusion, acetate is not involved in the differentiation or inhibition of lipolysis in adipocytes. And the decrease of adipose lipolysis does not decrease the density and proliferation of cancer cells.