Effects of rat bone marrow-derived mesenchymal stem cells on breast cancer cells with differing hormone receptor status

摘要

Breast cancer is a heterogeneous disease that can be classified into several molecular intrinsic subtypes according to hormone markers, including estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2. Breast cancer cases with different hormone status vary with respect to patient morbidity, metastasis organotropism and disease progression. It is well known that the most preferential relapse site of breast cancer is in the bone, but the metastatic incidence is markedly higher in hormone receptor-positive cancer compared with that in hormone receptor-negative cancers. Bone marrow-derived mesenchymal stem cells (BMSCs) perform important roles at the site of metastasis; however, the effects in different tumors or tumor subtypes are controversial. The present study aimed to explore the various effects of BMSCs on the biological characteristics of different hormone receptor statuses. BMSCs were obtained from female rats and characterized by cell lineage-specific antigens. The MCF-7 and MDA-MB-231 breast cancer cell lines, which are hormone receptor-positive and -negative, respectively, were employed in the present study. The cancer cells were co-cultured with BMSCs, and changes in the biological characteristic of cell growth, apoptosis, migration and epithelial-mesenchymal transition (EMT) were assessed. BMSCs exhibited chemotactic attraction to MCF-7, promoted the proliferation of MCF-7 cells and reduced MCF-7 cell apoptosis. By contrast, BMSCs exerted no marked effects on these behaviors of MDA-MB-231 cells. However, following co-culture with BMSCs, the migratory ability was enhanced in the two cell lines. Furthermore, the expression of epithelial markers (epithelial-cadherin and occludin) was decreased, and mesenchymal marker vimentin was markedly increased in the two cell lines. Notably, the migratory ability of MDA-MB-231 cells was attenuated compared with that of MCF-7 cells. The results from the present study indicated that BMSCs may favor receptor-positive cancer cell proliferation in bone and promote enhanced invasiveness of receptor-negative compared with receptor-positive cancer cells.