Macrophages Induce Endocrine Resistance in Breast Cancer Cells

ANDRÉS M. CASTELLARO; BEATRIZ L. CAPUTTO; GERMÁN A. GIL

Mar del Plata

Congreso; SAIB; 2015

Despite the clinical benefit of endocrine therapies for breast cancer, a significant proportion of patients develop resistance. Tumor associated macrophages (TAMs) promote tumor growth, but it is not known if they play a role in endocrine resistance. Here we report that TAMs promote proliferation, migration and invasiveness of breast cancer cells. TAMs also generate resistance to estrogen withdrawal or treatments with SERMs as tamoxifen or ICI in estrogen-dependent breast cancer cells. Furthermore, was observed in mice that the microenvironment formed by macrophages also increased breast tumor growth and tamoxifen resistance. We showed that both signaling pathways NF-κB and IL-6 are required for these responses, which include macrophage-mediated phosphorylation of the estrogen receptor alpha (ER-α), and the activation of proliferative and pro-inflammatory genes in breast cancer cells. Strikingly, the knockdowns of any of the three transcription factors STAT3, ER-α or NF-kB in MCF-7 cells inhibit proliferation and macrophages-induced endocrine resistance.Therefore, targeting both the ER and NF-κB pathways blocks macrophages-mediated endocrine resistance in breast cancer, offering a novel mechanism and great opportunities for use in prevention and treatment of refractory breast cancer.