This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Calvani, M. Articles by Melillo, G. Search for Related Content PubMed PubMed Citation Articles by Calvani, M. Articles by Melillo, G.

Differential Involvement of Vascular Endothelial Growth Factor in the Survival of Hypoxic Colon Cancer Cells

¹ Developmental Therapeutics Program, ² SAIC Frederick, Inc., and ³ Center for Cancer Research, National Cancer Institute-Frederick, Frederick, Maryland

Requests for reprints: Giovanni Melillo, DTP-Tumor Hypoxia Laboratory, Building 432, Room 218, National Cancer Institute at Frederick, Frederick, MD 21702. Phone: 301-846-5050; Fax: 301-846-6081; E-mail: melillog{at}ncifcrf.gov.

The recent approval of bevacizumab (Avastin), a humanized anti–vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with chemotherapy for the treatment of patients with metastatic colorectal cancer, has provided proof of principle of the efficacy of antiangiogenic strategies for cancer therapy. The activity of bevacizumab is primarily attributed to its ability to inhibit endothelial cell survival. Whether anti-VEGF strategies may also have a direct effect on cancer cell survival is poorly understood. We show that serum-starved colon cancer cells differentially respond to autocrine production of VEGF with the induction of hypoxia inducible factor-1 (HIF-1) and survival under hypoxic conditions. Inhibition of VEGF or VEGF receptor 2 (VEGFR2)/KDR, but not VEGFR1/Flt-1, was sufficient to abrogate VEGF-mediated induction of HIF-1 and survival in sensitive HCT116, but not in resistant HT29, colon cancer cells. These results provide evidence that a VEGF/KDR/HIF-1 autocrine loop differentially mediates survival of hypoxic colon cancer cells, and they suggest that colon cancer cells may be intrinsically sensitive or resistant to anti-VEGF strategies, which may determine the therapeutic efficacy of bevacizumab. [Cancer Res 2008;68(1):285–91]

This article has been cited by other articles:

				M. I. Koukourakis, A. Giatromanolaki, H. Sheldon, F. M. Buffa, G. Kouklakis, I. Ragoussis, E. Sivridis, A. L. Harris, and for the Tumour and Angiogenesis Research Group Phase I/II Trial of Bevacizumab and Radiotherapy for Locally Advanced Inoperable Colorectal Cancer: Vasculature-Independent Radiosensitizing Effect of Bevacizumab Clin. Cancer Res., November 15, 2009; 15(22): 7069 - 7076. [Abstract] [Full Text] [PDF]

				A. Torkamani and N. J. Schork Identification of rare cancer driver mutations by network reconstruction Genome Res., September 1, 2009; 19(9): 1570 - 1578. [Abstract] [Full Text] [PDF]

				P. Bendinelli, E. Matteucci, P. Maroni, and M. A. Desiderio NF-{kappa}B Activation, Dependent on Acetylation/Deacetylation, Contributes to HIF-1 Activity and Migration of Bone Metastatic Breast Carcinoma Cells Mol. Cancer Res., August 1, 2009; 7(8): 1328 - 1341. [Abstract] [Full Text] [PDF]