chemoattractant signaling between tumor cells and macrophages regulates cancer cell migration, metastasis and neovascularization化学引诱物肿瘤细胞和巨噬细胞之间的信号调节癌细胞迁移,转移和新血管形成.pdfVIP

Chemoattractant Signaling between Tumor Cells and Macrophages Regulates Cancer Cell Migration, Metastasis and Neovascularization 1¤ 1 1 2 1 2 Chad E. Green , Tiffany Liu , Valerie Montel , Gene Hsiao , Robin D. Lester , Shankar Subramaniam , 1 1 Steven L. Gonias , Richard L. Klemke * 1 Department of Pathology and Moores Cancer Center, University of California San Diego, La Jolla, California, United States of America, 2 Department of Bioengineering, University of California, San Diego, La Jolla, California, United States of America Abstract Tumor-associated macrophages are known to influence cancer progression by modulation of immune function, angiogenesis, and cell metastasis, however, little is known about the chemokine signaling networks that regulate this process. Utilizing CT26 colon cancer cells and RAW 264.7 macrophages as a model cellular system, we demonstrate that treatment of CT26 cells with RAW 264.7 conditioned medium induces cell migration, invasion and metastasis. Inflammatory gene microarray analysis indicated CT26-stimulated RAW 264.7 macrophages upregulate SDF-1a and VEGF, and that these cytokines contribute to CT26 migration in vitro. RAW 264.7 macrophages also showed a robust chemotactic response towards CT26-derived chemokines. In particular, microarray analysis and functional testing revealed CSF-1 as the major chemoattractant for RAW 264.7 macrophages. Interestingly, in the chick CAM model of cancer progression, RAW 264.7 macrophages localized specifically to the tumor periphery where they were found to increase CT26 tumor gro