CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer

Dingzhi Wang, Haibin Wang, Joanne Brown, Takiko Daikoku, Wei Ning, Qiong Shi, Ann Richmond, Robert Strieter, Sudhansu K. Dey, Raymond N. DuBois

Research output: Contribution to journalArticle

240 Scopus citations

Abstract

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 α), 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.

Original languageEnglish (US)
Pages (from-to)941-951
Number of pages11
JournalJournal of Experimental Medicine
Volume203
Issue number4
DOIs
StatePublished - Apr 17 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Wang, D., Wang, H., Brown, J., Daikoku, T., Ning, W., Shi, Q., Richmond, A., Strieter, R., Dey, S. K., & DuBois, R. N. (2006). CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer. Journal of Experimental Medicine, 203(4), 941-951. https://doi.org/10.1084/jem.20052124