Tumors are dependent upon new blood vessel formation, or angiogenesis, for expansive growth. Our recent analysis of gene expression led to the identification of several genes upregulated in endothelial cells that line tumor blood vessels, called Tumor endothelial markers (TEMs). However, further investigation of these genes has revealed that most are also present during normal physiological angiogenesis, for example, during wound healing and corpus luteum formation. In order to identify TEMs that are more confined to tumor endothelium, we plan to compare gene expression patterns of endothelial cells isolated from either regenerating liver (normal physiological angiogenesis) or liver metastasis (tumor angiogenesis). Towards this end, we have recently developed techniques that have enabled us to isolate endothelial cells from these tissues in mice. We will use Serial Analysis of Gene Expression (SAGE) technology to compare gene expression profiles, and then compare lead candidates to our human endothelial cell SAGE libraries to identify those which are also overexpressed in human tumor endothelium. These studies should enable us to identify new targets of tumor blood vessels that, hopefully, will have fewer cross reactivity's to normal tissues.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010486-04
Application #
7338628
Study Section
(MCGP)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2006
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Seaman, Steven; Stevens, Janine; Yang, Mi Young et al. (2007) Genes that distinguish physiological and pathological angiogenesis. Cancer Cell 11:539-54