Bone morphogenetic protein 2 increasing epithelial to mesenchymal transition in breast cancer cells with pausing of its proliferation

Substantial studies pointed the dual role of BMP-2 in tumorigenesis similar to TGF beta. Past studies documented that TGF beta mostly behaves as a tumor suppressor in case of early stage of a tumor but it often promotes tumorigenic potential in the advanced stage of a tumor. But, the precise role of BMP-2 in tumorigenesis is still opaque. This present study demonstrated that recombinant BMP2 (rh-BMP-2) treatment significantly increased cell migration in breast cancer MDA-MB-231 and MCF-7 cells. It might also augment epithelial to mesenchymal transition (EMT) of breast cancer cells since rh-BMP-2 increased expressions of mesenchymal markers (e.g. vimentin, Ncadherin and Zeb1) with simultaneous decrease of epithelial marker E-cadherin expression. In addition, BMP-2 enhanced expression and activity of matrix metalloproteinases (MMPs). However, BMP-2 significantly decreased cell proliferation in breast cancer cells with parallel inhibition of cell survival genes BCL2 and Bcl-xL transcripts, and cell cycle markers cyclin D1 and CDK2 expressions. These findings proposed that BMP-2 might augment metastatic cascade by pausing cell proliferation in breast cancer.