| First Author | Korsisaari N | Year | 2007 |
| Journal | Proc Natl Acad Sci U S A | Volume | 104 |
| Issue | 25 | Pages | 10625-30 |
| PubMed ID | 17553957 | Mgi Jnum | J:122262 |
| Mgi Id | MGI:3713934 | Doi | 10.1073/pnas.0704213104 |
| Citation | Korsisaari N, et al. (2007) From the Cover: Inhibition of VEGF-A prevents the angiogenic switch and results in increased survival of Apc+/min mice. Proc Natl Acad Sci U S A 104(25):10625-30 |
| abstractText | Anti-VEGF-A monoclonal antibodies, in combination with chemotherapy, result in a survival benefit in patients with metastatic colorectal and non-small cell lung cancer, but little is known regarding the impact of anti-VEGF-A therapy on benign or premalignant tumors. The Apc(+/min) mice have been widely used as a model recapitulating early intestinal adenoma formation. To investigate whether tumor growth in Apc(+/min) mice is mediated by VEGF-A-dependent angiogenesis, we used two independent approaches to inhibit VEGF-A: monotherapy with a monoclonal antibody (Mab) targeting VEGF-A and genetic deletion of VEGF-A selectively in intestinal epithelial cells. Short-term (3 or 6 weeks) treatment with anti-VEGF-A Mab G6-31 resulted in a nearly complete suppression of adenoma growth throughout the small intestine. Growth inhibition by Mab G6-31 was associated with a decrease in vascular density. Long-term (up to 52 weeks) treatment with Mab G6-31 led to a substantial increase in median survival. Deletion of VEGF-A in intestinal epithelial cells of Apc(+/min) mice yielded a significant inhibition of tumor growth, albeit of lesser magnitude than that resulting from Mab G6-31 administration. These results establish that inhibition of VEGF-A signaling is sufficient for tumor growth cessation and confers a long-term survival benefit in an intestinal adenoma model. Therefore, VEGF-A inhibition may be a previously uncharacterized strategy for the prevention of the angiogenic switch and growth in intestinal adenomas. |
