PROSTADIPE

Persistent organic pollutants are lipophilic chemicals that are present in many industrial products and accumulate throughout the food chain. From fetal life to adulthood we are chronically exposed to these pollutants. Some of them, called endocrine disrupting chemicals (EDCs), have been shown to interfere with the body’s endocrine system and produce adverse effects by modifying hormone regulation. In particular, EDCs seem to be implicated in the increased occurrence of some hormone-dependent cancers, including prostate cancers.

Due to their specific chemical structure, EDCs are not metabolizable and they thus accumulate in human adipose tissue. Doing so, they progressively make the adipose tissue a persistent internal source of systemic chronic exposure to EDCs. On the other hand, excess adiposity in obesity increases the risk of cancer development. In many tumors, the cells that form adipose tissue (adipocytes) are in close contact with the cancer cells. While adipocytes usually secrete various substances known as the “secretome” (which includes fatty acids, cytokines, exosomes, etc.), their secretion is modified in peri-tumoral adipose tissue. Moreover, the modified secretome seems to favor tumor growth.

We hypothesize here that exposure to EDCs contributes to modify the secretome of peri-tumoral adipose tissue in case of prostate cancer. To examine this hypothesis, we are investigating: 1) the EDC storage and release capacity of human adipocytes; 2) how EDCs modify the secretome of human adipocytes; 3) whether the modified adipocyte secretome influences the aggressiveness of prostate cancer tumoral cells.

To address these questions, we use human adipocytes (differentiated adipose-derived multipotent stem cells) and human prostate cells affected by cancer (carcinoma type), and put them in contact with different EDCs. Our preliminary results show that one of the EDCs is stored in the adipocytes in less than 24h, after one or more nanomolar doses. In the case of two EDCs, we observe increased prostate cancer cell proliferation when the cells are incubated with the supernatant from EDC pretreated adipocytes (conditioned media). We are in the process of analyzing the adipocyte secretome to identify how it has been modified. So far, we have shown that neither of the two EDCs modified fatty acid release by the adipocytes. Therefore, the EDC-induced secretome changes are to be found in other substances.