Impact of adipocytes and their secretome on the effectiveness of hormone therapy in breast cancer associated with overweight

Obesity, an established risk factor for breast cancer in postmenopausal women, is also responsible for higher rates of recurrence and mortality. In this context, our work evaluates the impact of the adipocyte secretome (AS) in the lesser response to hormone therapy. For this, 1 / mammary cancer cells were either co-cultured with human adipose stem cells (hASC) (hMAD cell line) differentiated into mature adipocytes (MA) or cultured in the presence of hMAD conditioned media (CM), and then treated or not with an anti-estrogen treatment (anti-E, Tamoxifen Tx or Fulvestrant Fv). Cell proliferation was measured by a fluorescence test using resazurin (Fluoroskan Ascent FL®, n=3) and followed in real time by impedancemetry (iCELLigence, n=3). 2 / The impact of overweight was assessed ex vivo using differentiated MAs from ASC of thin or obese women cultured in the presence of MCF-7 and Fv. In our different models, AS was able to increase the proliferation of MCF-7 cells, positive for the estrogen receptor (ER+), and to totally inhibit the antiproliferative effect of Tx and Fv. The use of MDA-MB-231 (RE- cells) showed that AS increased cell proliferation and counteracted the antiproliferative effect of Tx but not Fv. These results suggest that the observed effects were not exclusively mediated through the ER pathway. On the other hand, using AMs of thin and obese women, only the obese women AS could decrease the efficacy of the Fv. This effect was accompanied by an increase in the expression of the OB-R gene. Thus, these preliminary results suggest that AS could reduce the effectiveness of hormone therapy, and more markedly in the case of overweight. This could contribute to the tumor escape process and to the majored risk of recidive in overweight situation. Project funded by INCA, Mammadipo Project N° 666