TAMs Induce Endocrine Resistance and Stem Cell-Like Enrichment in Breast Cancer Cells

CASTELLARO AM; GIL GA

Córdoba

Congreso; LII Reaunión Anual de SAIB; 2016

It has been observed that tumor associated macrophages (TAMs) cause a marked increase in the proliferative capacity of MCF-7 cells and promote the growth of bigger breast tumors when MCF-7 cells are co-injected with TAMs in immunocompromised mice. We have found that crosstalk between MCF-7 cells and TAMs induce a number of alterations in the breast cancer cells, which can be grouped into two main facts. First, TAMs lead to the acquisition of a stem cell-like phenotype with higher metastatic potential and mesenchymal properties. This phenotype is characterized by the loss of the surface marker CD24. Thus, the normal population of MCF-7 cells that is CD24+ / CD44+ shifts to CD24- /CD44+.Secondly, the interaction between TAMs and MCF-7 cells, which are estrogen-dependent, entails to the development of resistance to estrogen withdrawal or treatments with selective ER modulators (SERMs) as Tamoxifen or ICI in MCF-7 cells.Moreover, the signaling pathways of both the NF-κB and IL-6/STAT3 are required for these responses which include macrophage-mediated phosphorylation of the estrogen receptor ER-α, and activation of proliferative and proinflammatory genes in the breast cancer cells. Indeed, the knockdown of any of these pathways such as STAT3, ER-α or NFkB in MCF-7 cells, could inhibit proliferation and the endocrine resistance induced by TAMs.