The role of tumor-associated macrophage in tumor progression.
ABSTRACT The tumor progression is not only regulated by metastasis promoting and suppressing genes in cancer cells but it is also strongly influenced by the interaction between cancer cells and the stromal cells. An abundance of inflammatory mediators and leukocytes has been known to promote cancer metastasis, and tumor associated macrophages (TAM) are the key players in the link between inflammation and cancer. TAM are derived from peripheral blood monocytes that are recruited into the tumor by inflammatory chemokines. Upon activation by cancer cells, TAM gain the ability of pro-tumoral functions including expression of various growth factors, promotion of angiogenesis and suppression of adaptive immunity, and many of these factors also play critical roles in cancer metastasis. In this review, we will summarize the recent information about the function of TAM in the inflammatory micro-environment of solid tumors and discuss the potential targets for future therapeutic approaches.
- SourceAvailable from: Yun-Sok Ha[show abstract] [hide abstract]
ABSTRACT: 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.Cancer Research 04/2013; · 8.65 Impact Factor