The vascular endothelial growth factor (VEGF) is known to contribute to breast carcinoma progression by promoting angiogenesis. The current studies address a novel function for VEGF in promoting the invasion and migration of breast carcinoma cells. Specifically, this proposal addresses the hypothesis that VEGF secretion by breast carcinoma cells promotes their invasion by binding to VEGF receptors on the same or neighboring tumor cells. Moreover, it is hypothesized that this VEGF autocrine signaling contributes to breast carcinoma invasion by promoting the PI3-kinase-dependent migration of these cells. Using an antisense strategy, the effects of inhibiting VEGF expression on the invasion and migration of breast carcinoma cells in vitro will be explored. Moreover, the hypothesis that this autocrine signaling drives breast carcinoma invasion and migration by maintaining constitutively elevated levels of PI3-kinase activity in these cells will be explored. Finally, a role for the VEGF receptor neuropilin in this VEGF autocrine function will be examined. Specifically, the effects of neuropilin inhibitory antibodies, as well as deletion constructs that inhibit endogenous neuropilin function on breast carcinoma invasion and migration will be investigated. Finally, I will assess the effects of specifically inhibiting VEGF autocrine signaling in breast carcinoma cells on their growth and metastasis in immunodeficient mice. The characterization of this novel VEGF function will be critical in broadening our knowledge of the multiple steps involved in breast carcinoma progression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01CA093855-04
Application #
6919224
Study Section
Subcommittee G - Education (NCI)
Program Officer
Eckstein, David J
Project Start
2002-07-01
Project End
2005-08-17
Budget Start
2005-07-01
Budget End
2005-08-17
Support Year
4
Fiscal Year
2005
Total Cost
$22,329
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
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