Blocking Vascular Hyperpermeability, the Initiation Step of Tumor Angiogenesis Inhibits Mammary Tumor
Final rept. 30 Sep 2000-30 Sep 2002
BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
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Mammary tumors growth, like most of the other solid tumors, beyond minimal size requires the generation of new blood vesseles and other stromal elements. It is generally agreed that vascular permeability factor vascular endothelial growth factor VPFVEGF is thought to be largely responsible for the hyperpermeability of tumor blood vessels. Information accumulating from different laboratories including ours has indicated that tumor angiogenesis and stroma formation develop sequentially as increased microvascular permeability triggered by VPFVEGF secreted mainly by the tumor. This seems to be the key initiation Step of angiogenesis. We have developed three projects related to angiogenesis. a We have generated mutant forms of VPFVEGF into adneovirus vector but initial experiments in animals model did not reproduce the in vitro results as we postulated. b We have defined the central role of p53 on regulation of VEGF in breast cancer cells and also evaluated how does p53 modulate the protooncogene c-Src in this pathway. c Finally, a project is ongoing to develop an effective anti-tumor angiogenic immunity by means of DC-based vaccination at the same time it is also directed toward an understanding of the effect of VEGF on DC function. Our hypothesis is that DCs expressing a non-secreted form of VEGF endogenously are capable, of evoking anti-angiogenic immunity in breast cancer, upon injection as a vaccine, in the host.
- Anatomy and Physiology
- Medicine and Medical Research