The proposed research in this application is aimed at understanding a specific anti-tumor immunity in prostate cancer using animal models. The transformation-induced major histocompatibility (MHC) I chain-related molecule (MIC) is shown to be expressed on most epithelial tumors, including prostate carcinoma. MIC is identified as a ligand for NKG2D, a stimulatory immune receptor expressed by all human natural killer (NK) and cytotoxic T cells. Engagement of MIC to NKG2D triggers NK cell and augments T cell anti-tumor immunity. Surface expression of MIC on transformed cells is proposed to mark nascent tumors for immune surveillance. Studies have shown that advanced cancer cells produce two forms of MIC, the surface membrane-bound MIC and the soluble form of MIC (sMIC). It has been shown that siMIC mediates deficiency in MIC-NKG2D mediated anti-tumor immunity. Compelling clinical studies in prostate cancer have demonstrated that levels of serum sMIC increase in advanced cancers. It is unknown whether sMIC allows a lower grade tumor to become more aggressive or whether the progression to a more aggressive phenotype causes the production of sMIC. The long-term goal of this proposed research is to delineate the relationship between levels of sMIC and prostate cancer progression and to define and validate strategies to counteract tumor production of sMIC. To achieve this long-term goal, this proposed research aims specifically at establishing an animal model to further study these clinical observations in prostate cancer. Outcomes from this proposed research would potentially have direct clinical implication for treatment of prostate cancer. Furthermore, as studies have shown that sMIC was also produced in other epithelial tumors, such as breast, lung, and colon cancers, the outcomes of this proposed research will also have broad clinical implications in other epithelial tumors. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01CA116002-04
Application #
7480339
Study Section
Subcommittee G - Education (NCI)
Program Officer
Lohrey, Nancy
Project Start
2005-09-15
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
4
Fiscal Year
2008
Total Cost
$153,306
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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