Tumors are dependent upon new blood vessel formation, or angiogenesis, for expansive growth. Our prior analysis of gene expression led to the identification of several genes upregulated in endothelial cells that line tumor blood vessels, called TEMs. Two of these, TEM5 and TEM8 encode products that are of particular interest because they reside on the cell surface and may therefore be directly accessible to blood-borne therapeutics. In an attempt to understand the functional role of these genes in angiogenesis, we have generated TEM5 and TEM8 knockout mice. By challenging the gene disrupted mice with tumors, we are evaluating the importance of these genes in tumor angiogenesis. These studies are also enabling us to better understand the normal physiological function of these genes particularly as it relates to angiogenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010484-09
Application #
8349020
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2011
Total Cost
$302,092
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Andersen, N J; Boguslawski, E A; Naidu, A S et al. (2016) Anthrax Toxin Receptor 1 Is Essential for Arteriogenesis in a Mouse Model of Hindlimb Ischemia. PLoS One 11:e0146586
Emenaker, Nancy J; Zudaire, Enrique; St Croix, Brad (2014) Chemoprevention of metastasis. Oncotarget 5:6556-7
Kuo, Frank; Histed, Stephanie; Xu, Biying et al. (2014) Immuno-PET imaging of tumor endothelial marker 8 (TEM8). Mol Pharm 11:3996-4006
Chaudhary, Amit; Hilton, Mary Beth; Seaman, Steven et al. (2012) TEM8/ANTXR1 blockade inhibits pathological angiogenesis and potentiates tumoricidal responses against multiple cancer types. Cancer Cell 21:212-26
Yang, Mi Young; Chaudhary, Amit; Seaman, Steven et al. (2011) The cell surface structure of tumor endothelial marker 8 (TEM8) is regulated by the actin cytoskeleton. Biochim Biophys Acta 1813:39-49
Cullen, Mike; Elzarrad, Mohammed K; Seaman, Steven et al. (2011) GPR124, an orphan G protein-coupled receptor, is required for CNS-specific vascularization and establishment of the blood-brain barrier. Proc Natl Acad Sci U S A 108:5759-64
Cullen, Mike; Seaman, Steven; Chaudhary, Amit et al. (2009) Host-derived tumor endothelial marker 8 promotes the growth of melanoma. Cancer Res 69:6021-6