Breast Tissue Stromal Cells Preferentially Promote Generation of M2 Macrophages: A Novel Mechanism for Tumor Supportive Properties of Breast Microenvironment

摘要

Our goals were: (1) to investigate the effect of tissue-specific stromal cells, i.e. mesenchymal stromal/stem cells (MSCs) and macrophages (MQs), on growth of breast tumor cells, and (2) to test the hypothesis that MSCs of non-breast adipose tissues, in contrast to MSCs of breast tissues, precludes such tissues from becoming a site for breast cancer metastasis. We generated MSCs from normal breast and abdominal adipose tissues with phenotypic charcteristic similar to bone marrow (BM) MSCs. Only inflammatory cytokine IL1b was expressed at a higher level in abdominal MSCs compared to breast MSCs. MSCs alone, monocyte derived MQs alone, or combined together increased proliferation of MCF7 breast cancer cell line. However, only addition of MQs to BM-MSCs caused a higher level of proliferation of MCF7 cells compared to MSCs alone, suggesting the potential role of BM-MSCs in breast cancer metastasis to bone. MQs co-cultured with breast or abdominal adipose MSCs expressed a higher level of VEGF A, VEGF C, SERPINE1 and FGF2 compared to MQs alone. However, the differences between two MSCs were not statistically significant, possibly because MSCs important in breast cancer growth might not be originating from breast adipose tissue but from ductal/periductal stromal components. Another explanation might be that we derived MSCs from normal, and not cancerous, breast tissues. We propose investigating the biology of subcutaneous adipose tissue, the largest human tissue and the least receptive to breast cancer metastasis, as a novel approach to find more effective therapeutic options for breast cancer.