Dysregulated BMPs expression may contribute to the development and progression of renal cell carcinoma (RCC). Herein, we report that bone morphogenetic protein-6 (BMP-6) promotes the proliferation of RCC cells by IL-10-mediated polarization of tumor-associated macrophages (TAM). IL-10 secretion from macrophages stimulated by BMP-6 required nuclear interaction between Smad5 and STAT3. Examination of human RCC specimens revealed a three-marker signature composed of BMP-6, IL-10, and CD68 (macrophages) that was associated with a significantly higher probability of dying from cancer. In particular, patients with elevated serum levels of IL-10 had a significantly higher rate of metastasis within 5 years after surgery. Together our results suggested that BMP-6/macrophage/IL-10 autocrine loop regulates M2 polarization of TAMs in RCC and that the disruption of this loop may offer an RCC therapeutic strategy.
- Received December 19, 2012.
- Revision received March 25, 2013.
- Accepted March 28, 2013.
- Copyright © 2013, American Association for Cancer Research.