Differential involvement of vascular endothelial growth factor in the survival of hypoxic colon cancer cells

Maura Calvani, Daniela Trisciuoglio, Cristina Bergamaschi, Robert H. Shoemaker, Giovanni Melillo

Research output: Contribution to journalArticle

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Abstract

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-1α (HIF-1α) 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-1α and survival in sensitive HCT116, but not in resistant HT29, colon cancer cells. These results provide evidence that a VEGF/KDR/HIF-1α autocrine loop differentially mediates survival of hypoxic colon cancer cells, and they suggest that colon cancer cells maybe intrinsically sensitive or resistant to anti-VEGF strategies, which may determine the therapeutic efficacy of bevacizumab.

Original languageEnglish
Pages (from-to)285-291
Number of pages7
JournalCancer Research
Volume68
Issue number1
DOIs
Publication statusPublished - Jan 1 2008

Fingerprint

Colonic Neoplasms
Vascular Endothelial Growth Factor A
Survival
Hypoxia-Inducible Factor 1
Cell Survival
Vascular Endothelial Growth Factor Receptor-2
Combination Drug Therapy
Colorectal Neoplasms
Neoplasms
Therapeutics
Endothelial Cells
Monoclonal Antibodies
Bevacizumab
Serum

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Differential involvement of vascular endothelial growth factor in the survival of hypoxic colon cancer cells. / Calvani, Maura; Trisciuoglio, Daniela; Bergamaschi, Cristina; Shoemaker, Robert H.; Melillo, Giovanni.

In: Cancer Research, Vol. 68, No. 1, 01.01.2008, p. 285-291.

Research output: Contribution to journalArticle

Calvani, Maura ; Trisciuoglio, Daniela ; Bergamaschi, Cristina ; Shoemaker, Robert H. ; Melillo, Giovanni. / Differential involvement of vascular endothelial growth factor in the survival of hypoxic colon cancer cells. In: Cancer Research. 2008 ; Vol. 68, No. 1. pp. 285-291.
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