Growing evidence indicates that obesity is associated with increased cancer risk and negatively impacts cancer recurrence and survival. Adipose tissue (AT) is frequently found at close proximity to invasive primary solid tumours including breast and prostate cancer as well as in bone metastatic sites. Main function of adipocytes, the metabolically active cells of AT, is to store lipids and to deliver them, when needed, to energy demanding tissues. Adipocytes are also active endocrine cells that secrete a large variety of molecules including growth factors, chemokines and pro-inflammatory molecules.

Although AT share common features, each fat depot exhibits metabolic and secretory specificities. Thus, the use of human AT close to each type of tumor is key to the relevance of our results. The strong collaboration that we established since several years with clinicians allow us to work with human fat depots (mammary AT, periprostatic AT, bone-marrow AT). Some of the clinicians are members of the team and we welcome each year medical residents under training.

We have demonstrated that tumor-surrounding adipocytes promote aggressiveness by secreting soluble factors such as chemokines, pro-inflammatory cytokines and by modulating tumor cell metabolism. One of the most specific and emerging mechanism regarding the role of mature adipocytes in the tumor microenvironment involves the ability of cancer cells to advantageously exploit the nourishing role of adipocytes. At primary tumor sites, tumor cells induce lipolysis in adipocytes leading to the release free fatty acid (FFA) or contained in extra-cellular-vesicles that are taken up by tumor cells. These FFA trigger a complex metabolic remodeling in cancer cells increasing their survival, invasive and metastatic abilities as well as resistance to treatment. Aside this metabolic crosstalk, in prostate cancer, we are investigating the role of abundant PPAT (that accumulates independently of body mass index) in prostate cancer progression, a project that highlights the central role of extra-cellular matrix remodeling.

The team possesses national and international recognition as assessed by our 5 highly cited papers (Top 1 % Web of Science in Clinical Science) in the field of adipose tissue and cancer (Dirat et al. 2011 Cancer Research ; Bochet et al. 2013 Cancer Res ; Lazar et al. 2016 Cancer Res ; Laurent et al. Nat Commun, 2016 ; Wang et al. 2017 JCI Insight).