Cancers, Vol. 11, Pages 189: Tumor-Associated Macrophages Induce Endocrine Therapy Resistance in ER+ Breast Cancer Cells

Cancers, Vol. 11, Pages 189: Tumor-Associated Macrophages Induce Endocrine Therapy Resistance in ER+ Breast Cancer Cells Cancers doi: 10.3390/cancers11020189 Authors: Castellaro Rodriguez-Baili Di Tada Gil Antiestrogenic adjuvant treatments are first-line therapies in patients with breast cancer positive for estrogen receptor (ER+). Improvement of their treatment strategies is needed because most patients eventually acquire endocrine resistance and many others are initially refractory to anti-estrogen treatments. The tumor microenvironment plays essential roles in cancer development and progress; however, the molecular mechanisms underlying such effects remain poorly understood. Breast cancer cell lines co-cultured with TNF-α-conditioned macrophages were used as pro-inflammatory tumor microenvironment models. Proliferation, migration, and colony formation assays were performed to evaluate tamoxifen and ICI 182,780 resistance and confirmed in a mouse-xenograft model. Molecular mechanisms were investigated using cytokine antibody arrays, WB, ELISA, ChIP, siRNA, and qPCR-assays. In our simulated pro-inflammatory tumor microenvironment, tumor-associated macrophages promoted proliferation, migration, invasiveness, and breast tumor growth of ER+ cells, rendering these estrogen-dependent breast cancer cells resistant to estrogen withdrawal and tamoxifen or ICI 182,780 treatment. Crosstalk between breast cancer cells and conditioned macrophages induced...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research