Oral and oropharyngeal squamous cell carcinomas (OSCC) account for nearly 8,000 deaths a year nationally, with South Carolina ranking the highest of the fifty states in oral cancer mortality. Significantly, the survival rate of 51% has not changed over the past thirty years. Because the mortality of OSCC directly relates to the stage of diagnosis, early detection techniques and targeted therapy are clearly needed for enhanced survival rates. A strong correlation exists between the IGF system and cancer; individuals with the highest serum levels of insulin-like growth factor-1 (IGF-1) have the highest incidence of prostate and breast cancer. IGF-1 and IGF-2 mediate their tumorigenic effects through activation of the IGF-1 receptor (IGF-1R). The IGFs also bind with high affinity to a family of soluble proteins known as the IGF binding proteins (IGFBPs), which reduce the bioavailability of the IGFs by sequestering them from the IGF-1R. The IGFBPs are natural inhibitors of the IGF system. As such, they are presently the only known IGF antagonists. Preliminary data suggest that the IGF system may be a target for therapeutics and prevention of OSCC. Our working hypothesis is that the amplification of the IGF system causing the overexpression of IGF-1R, IGF-1 or IGF-2, plays a central role in the molecular pathogenesis of OSCC. To test our hypothesis the following Specific Aims have been formulated:
Specific Aim 1 : Examine the expression of the IGF system components in model OSCC cell lines and human OSCC tissue, and Specific Aim 2: Determine the role of the C-terminus of lGFBP-2 in IGF binding. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DE015249-04
Application #
7111037
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Avila, Albert
Project Start
2003-09-30
Project End
2008-05-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
4
Fiscal Year
2006
Total Cost
$24,522
Indirect Cost
Name
Medical University of South Carolina
Department
Pharmacology
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Kibbey, Megan M; Jameson, Mark J; Eaton, Erin M et al. (2006) Insulin-like growth factor binding protein-2: contributions of the C-terminal domain to insulin-like growth factor-1 binding. Mol Pharmacol 69:833-45
Slomiany, Mark G; Black, Leigh Ann; Kibbey, Megan M et al. (2006) IGF-1 induced vascular endothelial growth factor secretion in head and neck squamous cell carcinoma. Biochem Biophys Res Commun 342:851-8