Macrophages Induce Tamoxifen Resistance in Breast Cancer

GIL GA; RODRIGUEZ-BAILI MC; CASTELLARO AM

Washington

Congreso; Reunión Anual de la American Association for Cancer Research; 2017

The microenvironment formed by macrophages induces both, epithelial mesenchimal transition in breast cancer cells with a stem cell?like phenotype and endocrine-resistant. This microenvironment induces proliferation, invasiveness, and migration of MCF-7 breast cancer cells, even in presence of the partial antiestrogen 4-hydroxytamoxifen or the pure antiestrogen ICI 182780. Furthermore, the in vitro results correlate perfectly with what is observed in vivo, where the microenvironment formed by macrophages increases tumor growth and resistance to 4-hydroxytamoxifen. We have shown that the co-culture of breast cancer cells MCF-7 with macrophages induces a sustained release of IL-6 and TNF-α from both cell types and that the stimulus with both cytokines is sufficient to MCF-7 proliferate. However, the proliferation rates achieved by MCF-7 cells co-cultured with macrophages are quite higher than those reached by MCF-7 cells cultured alone under the same mitogenic stimulus with IL-6 and TNF-α. Strikingly, the knockdown of any of the three transcription factors STAT3, ER-α or NF-kB in MCF-7 cells substantially inhibited the high rates of proliferation and the endocrine resistance that the co-culture with macrophages induces on them.