Prostate cancer (PCa) is the second most common form of solid tumor in men worldwide and the fifth leading cause of death from cancer. It is a highly heterogeneous disease, ranging from slow-growing indolent tumors to fatal metastatic carcinomas. Risk stratification is, therefore, the cornerstone for selecting the most appropriate treatment for these men.

The prostate is surrounded by a fat depot named periprostatic adipose tissue (PPAT) that is, like other fat depots, an active endocrine organ. We and others have shown that PPAT contribute to tumor progression through secretion of soluble factors and lipid mediators (reviewed in Estève et al. 2020 Curr Opin Endocr Met Res). Mature adipocytes from PPAT, through an original CCR3/CCL7 axis, favor the homing of cancer cells outside of the prostate gland. This effect is amplified in obesity and controls the local dissemination of prostate cancer in vivo (as shown using animal models and annotated collections of human cancers) (Laurent et al. 2016 Nat Commun). Once tumor cells have invaded the PPAT, FFAs liberated from adipocytes are taken up by tumor cells where they stimulate the expression of pro-oxidant enzymes leading to increased intra-cellular reactive oxygen species and invasive potential of tumor cells. Human tumor analysis revealed that pro-oxidant enzymes expression is highly upregulated at the tumor invasive front where cancer cells are in close proximity to adipocytes, this process being exacerbated by obesity, highlighting the clinical relevance of our results (Laurent et al. 2019 Mol Cancer Res).  Our work emphasizes the key role of adipocytes in prostate cancer local dissemination and proposes new molecular targets for the treatment of obese patients exhibiting aggressive diseases. We have reviewed the role of PPAT in prostate cancer dissemination (Estève et al. 2020 Curr Opin Endocr Met Res).