Ten genes that code for cell adhesion molecules have been identified by gene array analysis that are up-regulated in ovarian carcinoma tissue samples and are relatively specific to ovarian carcinoma. The objective of this project is to identify one or more cell adhesion molecule in which: (a) altered gene expression corresponds to altered protein expression, (b) protein expression is associated with patient information, and (c) the biological relevance of the molecules can be defined with respect to ovarian carcinoma. These molecules may potentially serve as early detection biomarkers or for detection of recurrence of ovarian carcinoma. In addition, these molecules may prove useful in the design of novel therapeutic regimens for ovarian carcinoma.
In Aim #1, the ten cell adhesion proteins will be localized by immunohistochemistry in tissue samples of ovarian carcinoma vs. other tissue types. Their molecular weight in tissue samples will be verified by Western immunoblotting or radioimmunoprecipitation.
In Aim #2, blood and ascites samples from patients with ovarian carcinoma will be screened for the presence of the proteins by Western immunoblotting or radioimmunoprecipitation. The level of each protein in the patients' circulation will be quantitated by ELISA or radioimmunoassay. Statistical analysis will be used to identify the association between tissue distribution, protein expression, and circulating levels of the proteins, and tissue histology and patient outcome/information.
In Aim #3, the levels of expression of the proteins on the surface and in the spent media of fresh ovarian carcinoma patient samples and established cell lines will be quantitated. The role of these cell adhesion proteins in ovarian carcinoma cell adhesion, invasion, and aggregate formation will be elucidated by use of blocking monoclonal antibodies and RNA interference. The association between levels of expression/secretion of the cell adhesion proteins with biological functional activities and patient information will be determined.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA106878-01A1
Application #
6924258
Study Section
Special Emphasis Panel (ZRG1-CBSS (01))
Program Officer
Lively, Tracy (LUGO)
Project Start
2005-05-01
Project End
2010-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
1
Fiscal Year
2005
Total Cost
$284,545
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pathology
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Skubitz, Keith M; Pambuccian, Stefan; Manivel, J Carlos et al. (2008) Identification of heterogeneity among soft tissue sarcomas by gene expression profiles from different tumors. J Transl Med 6:23

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