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 language | English |
|---|---|
| Pages (from-to) | 285-291 |
| Number of pages | 7 |
| Journal | Cancer Research |
| Volume | 68 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2008 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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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 journal › Article
}
TY - JOUR
T1 - Differential involvement of vascular endothelial growth factor in the survival of hypoxic colon cancer cells
AU - Calvani, Maura
AU - Trisciuoglio, Daniela
AU - Bergamaschi, Cristina
AU - Shoemaker, Robert H.
AU - Melillo, Giovanni
PY - 2008/1/1
Y1 - 2008/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=39149122201&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-5564
DO - 10.1158/0008-5472.CAN-07-5564
M3 - Article
C2 - 18172321
AN - SCOPUS:39149122201
VL - 68
SP - 285
EP - 291
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 1
ER -