Prostate cancer-derived CCN3 induces M2 macrophage infiltration and contributes to angiogenesis in prostate cancer microenvironment

摘要: // Po-Chun Chen 1,2 , Hsu-Chen Cheng 3 John Wang 4 Shin-Wei 5 Huai-Ching Tai 6,7 Chiao-Wen Lin 8,9 and Chih-Hsin Tang 1,10,11 1 Graduate Institute of Basic Medical Science, China University, Taichung, Taiwan 2 Department Research, Chung Shan University Hospital, Life Sciences, National Hsing Pathology, Taichung Veterans General Medicine, Mackay College, New Taipei City, 6 Urology, Taipei, 7 Clinical 8 Oral 9 Dentistry, 10 Pharmacology, School 11 Biotechnology, College Health Asia Correspondence: Tang, email: Lin, Keywords : CCN3; VEGF; Prostate cancer; M2 macrophage; angiogenesis Received November 4, 2013 Accepted February 2, 2014 Published Abstract Tumor-associated macrophages (TAMs) are M2-polarized that infiltrate the tumor microenvironment promote tumorigenesis. However, mechanisms by which TAMs modulate prostate cancer (PCa) growth poorly understood. Here, we found expression Nephroblastoma Overexpressed (NOV/CCN3) is upregulated in PCa cells correlated with macrophage infiltration. RAW264.7 migration was induced conditioned media (CM) from various proportion to cellular level CCN3 inhibited an anti-CCN3 neutralizing antibody. PCaCM treatment skewed cell differentiation M1 phenotype phenotype. PCa-derived focal adhesion kinase (FAK)/Akt/NF-κB signaling cells, resulted VEGF subsequently increased tube formation endothelial progenitor cells. Finally, PCa-secreted stimulated promoted chick chorioallantoic membrane assay (CAM), tumor-associated a xenograft mouse model. Our results indicate can recruit skew their In turn, CCN3-stimulated contribute VEGF-dependent angiogenesis. This study reveals novel mechanism enhance identifies potential therapeutic target for PCa.