We have found that loss of Vascular Endothelial Growth Factor-A expression in myeloid cells has profound and unexpected effects in a mouse model of breast cancer. Our recent findings illustrate how inflammatory cells act to induce vascular changes in tumors, and how these changes alter tumor perfusion and oxygenation, as well as tumor cell survival and malignant progression. The work proposed here will allow us to explore and exploit these new and novel findings, in order to: determine the mechanisms of myeloid cell interactions with endothelial cells during tumor angiogenesis;better understand the relationship between myeloid cell VEGF expression and metastasis;and determine how these findings could be used to increase the efficacy of chemotherapy.
The aims we propose to further our understanding of these phenomena are: 1: Determine the molecular mechanisms for differential VEGF signaling through innate immune cells in tumors. 2: Determine how VEGF expression from myeloid cells impacts metastasis. 3: Determine how VEGF from myeloid cells impacts chemotherapy delivery and efficacy. In sum, we believe this application will address key questions surrounding the processes of inflammation, angiogenesis, and tumor growth, with a particular emphasis on how these influence mammary tumorigenesis and metastasis.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01CA153983-04
Application #
8597539
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Woodhouse, Elizabeth
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Cambridge
Department
Type
DUNS #
City
Cambridge
State
Country
United Kingdom
Zip Code
CB2 1TN
Cowburn, Andrew S; Takeda, Norihiko; Boutin, Adam T et al. (2013) HIF isoforms in the skin differentially regulate systemic arterial pressure. Proc Natl Acad Sci U S A 110:17570-5