Impact of cancer cells on adipose tissue lipolysis, using precision-cut adipose tissue slices

Details

Supervisors

Debier, Cathy ; Bindels, Laure B.

Faculty

Faculté des bioingénieurs

Degree label

Master [120] : bioingénieur en sciences agronomiques, à finalité spécialisée

Abstract

It is now well established that cancer cells communicate with cells present in the tumor microenvironment, resulting in tumor promotion. Besides many functions such as energy storage or control of energy homeostasis, the implication of adipose tissue in the promotion of cancer has been recently discovered and seems interesting to target for cancer research. Among others, several types of cancer cells, including breast cancer, have been shown to induce lipolysis of the adipose tissue. Adipocyte lipolysis was thus labeled as a relevant pathway that potentially provides metabolic substrates to breast cancer cells. In vitro experiments are relevant in studying the interactions between breast cancer cells and adipose tissue since they offer the opportunity to screen numerous parameters to gain insight into key aspects of the adipose tissue environment, under controlled conditions. Among the in vitro methods commonly used to study the impact of cancer cells on adipose tissue function, the conditioned medium experiment is a relevant model. The principle is to incubate breast cancer cells with a specific medium that is then collected and transferred to adipocytes. Among multiple in vitro models, the technique of precision-cut adipose tissue slices (PCATS) was recently established in our lab using northern elephant seals and later adapted on pigs (Debier et al., 2020; De Jaeger, 2020; Pirard, 2019). The slices can be cultured for an extended period and this method allows to fully represent the environment and entire structure and functions of the whole adipose tissue. In 2021, a conditioned medium experiment was carried out in our lab using pig PCATS. The goal was to study the influence of breast cancer cells on adipose tissue lipolysis using this innovative model. A conditioned medium was generated by breast cancer cells and subsequently put into contact with pig PCATS to investigate its effect on lipolysis. In opposition to the increase of lipolysis reported with in vitro models involving murine adipose cells, a decrease of lipolysis was observed with pig PCATS. Given this context, the specific purpose of this master thesis was to investigate the reasons behind these contrasting results and explain why the lipolysis of PCATS was inhibited. Therefore, conditioned medium experiments have been carried out by focusing on three parameters that could influence the lipolysis of PCATS i.e. the presence of fetal bovine serum (FBS) and glutamine in the culture medium, and the incubation time used for the generation of conditioned medium. Our results globally showed that the lipolysis of PCATS was either inhibited or remained unchanged following contact with the different conditioned media. Neither the presence of FBS and glutamine in the conditioned medium, nor the incubation time used for its generation, showed any impact that could explain the inhibition of the lipolysis of PCATS. Potential hypotheses including the species-origin of the adipose tissue and breast cancer cells, the localization of the adipose tissue, the chosen method for the culture of adipose tissue or even the lipid state of the adipose tissue (lean or obese) are discussed.