Effect of truncated neurokinin-1 receptor expression changes on the interaction between human breast cancer and bone marrow-derived mesenchymal stem cells.

Abstract

Previous studies in breast cancer cell lines showed that truncated neurokinin receptor-1 (NK1R-Tr) was able to promote malignant transformation of breast cells, and NK1R-Tr may contribute to tumor progression and promote distant metastasis in human breast cancer. A co-culture model of breast cancer and bone marrow-derived human mesenchymal stem (HMSC-bm) cells showed that HMSC-bm inhibited the growth of breast cancer cells and entered the bone marrow at early stages. Down-regulation of NK1R-Tr may be a key factor in maintaining the quiescent phenotype of breast cancer cells among bone marrow stroma. Stromal-derived factor (SDF)-1α expression was negatively correlated with NK1R-Tr expression in breast cancer cells. Secretion of SDF-1α by HMSC-bm may maintain the quiescent phenotype of breast cancer cells among bone marrow stroma by down-regulating NK1R-Tr expression. Transforming growth factor (TGF)-β1 expression was positively associated with NK1R-Tr expression in breast cancer cells. In a co-culture system, MDA-MB-231-TGF-β1I (TGF-β genes were suppressed using specific shRNA) cells were able to attach to HMSC-bm quickly, indicating that TGF-β1 was also a key factor for maintaining the quiescent phenotype of breast cancer cells in bone marrow stroma. However, the detailed mechanism still remained unclear and could involve other molecules, in addition to NK1R-Tr.