NEW YORK (Reuters Health) - Vascular endothelial growth factor (VEGF) and its receptor 1 (VEGFR-1) play a central role in tumor angiogenesis, suggesting that “VEGFR-1 can serve as a target for ani-angiogenic gene therapy,” German researchers report in the September 1st issue of the International Journal of Cancer.
It is known that VEGFR-2 is a key regulator of angiogenesis in proliferating tumor epithelium, Dr. Georg Brier of the Institute for Pathology, Dresden, and colleagues note. His group examined the effect of VEGFR-1 in vascularization of experimental tumors.
The researchers generated VEGFR-1 mutants that lacked the intracellular tyrosine kinase domain. Retrovirus-mediated gene transfer of these mutants into mice with xenografted C6 gliomas and syngeneic BFS-1 fibrosarcoma led to a strong reduction in tumor growth and angiogenesis.
In particular, in fibrosarcoma there was reduced vascular density, decreased tumor cell proliferation as well as increased tumor cell apoptosis and the formation of necrosis.
Moreover, when full-length VEGFR-1 was transferred by the same means there was a significant reduction in growth in both types of tumor.
The fibrosarcoma cells were not infected by the retrovirus, indicating that the associated inhibitory processes were mediated via the host tumor endothelial cells, the investigators report.
Given these and other findings, the researchers conclude that VEGFR-1 is a “promising novel target for anti-angiogenic gene therapy.”
Source: Int J Cancer 2004;111:348-357. [ Google search on this article ]
MeSH Headings:Animal Diseases: Biological Therapy: Disease Models, Animal: Genetic Engineering: Genetic Techniques: Glioma: Investigative Techniques: Neoplasms: Neoplasms by Histologic Type: Neoplasms, Germ Cell and Embryonal: Neoplasms, Glandular and Epithelial: Neoplasms, Nerve Tissue: Therapeutics: Gene Therapy: Endothelial Growth Factors: Neuroectodermal Tumors: Neoplasms, Neuroepithelial: Analytical, Diagnostic and Therapeutic Techniques and Equipment: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
