CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer.

Wang D, Wang H, Brown J, Daikoku T, Ning W, Shi Q, Richmond A, Strieter R, Dey SK, DuBois RN
J Exp Med. 2006 203 (4): 941-51

PMID: 16567391 · PMCID: PMC2118273 · DOI:10.1084/jem.20052124

Chronic inflammation is a well-known risk factor for cancer. Proinflammatory mediators such as prostaglandin E2 (PGE2) promote colorectal tumor growth by stimulating angiogenesis, cell invasion, and cell growth, and inhibiting apoptosis. Molecules that regulate tumor-associated angiogenesis provide promising therapeutic targets for treatment of colorectal cancer (CRC) as indicated by the recent development of the novel anti-angiogenic agent bevacizumab (Avastin). However, use of this drug only prolongs survival by several months, highlighting the importance of finding more effective treatment regimens. We report here that PGE2 induces expression of CXCL1 (growth-regulated oncogene alpha), a pro-angiogenic chemokine, in human CRC cells. More importantly, CXCL1 released from carcinoma cells induces microvascular endothelial cell migration and tube formation in vitro. Furthermore, PGE2 promotes tumor growth in vivo by induction of CXCL1 expression, which results in increased tumor microvessel formation. These results have potential clinical significance because we found that CXCL1 expression correlates with PGE2 levels in human CRCs. Collectively, our findings show for the first time that CXCL1 is regulated by PGE2 and indicate that CXCL1 inhibitors should be evaluated further as potential anti-angiogenic agents for treatment of CRC.

MeSH Terms (22)

Adenoma Animals Caco-2 Cells Cell Line, Tumor Cell Movement Chemokine CXCL1 Chemokines, CXC Colorectal Neoplasms Dinoprostone Endothelium, Vascular ErbB Receptors Female Humans Intercellular Signaling Peptides and Proteins Male Mice Mice, Knockout Mice, SCID Mice, Transgenic Mitogen-Activated Protein Kinases Neovascularization, Pathologic Receptors, Interleukin-8B

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