Cluster designation (CD) molecules are cell surface antigens differentially expressed among the various cell types of our body. The major cell types of the prostate can be identified by their CD expression. The CD phenotype for prostate cancer cells is CD10-/CD13-CD24/CD26+/CD38/CD57+/CDw75+/CD107b+, found for many tumors examined. It is like the CD10+/CD13+/CD24+/CD26+/CD38+/CD57+/CDw75+/CD107b+ pattern of luminal cells save for CD10 and CD13, and very unlike the CD10-/CD13-/CD24-/CD26-/CD38+/CD57-/CDw75-/CD107b- pattern of basal cells. Hence, cancer cells differ from their normal counterpart in the absent expression of CD10 and CD13, increased expression of CD24, and diminished or absent expression of CD38. Variant cancer CD phenotypes such as cancer cells scored CD10+ are also found. About 25% of the primary tumors analyzed contain CD10+ cancer cells. And unlike primary tumors, all lymph node metastases analyzed to date have CD10+ cancer cells. Incidentally, node-derived cell line LNCaP and xenograft LuCaP 35 are both CD10+. Prostate tumors can therefore be characterized by their composition of cancer cell types, and accordingly their behavior is governed by these constituent cell types. The presence of certain cancer cell types would indicate a particular disease course (metastasis to lymph nodes, for example). Thus, cancer CD phenotypes can be used to stratify patients into different prognostic groups and to predict clinical outcome more accurately. While there is differential expression of CD molecules among the cancer cell types several CD molecules are found in almost all types, and these molecules can be targeted for cell killing as a means to treat disseminated disease. We propose to define prostate cell type compositions in putative premalignant lesions, primary tumors and metastases. This study has great potential towards better prostate cancer diagnosis and prognosis. An in vitro three-dimensional cell culture system will be used to study the effect of absent CD10 or CD13 expression in prostate epithelial cell differentiation. CD10 and CD13 are both peptidases and are likely involved in the processing of bioactive signaling peptides. Their absence might lead to the aberrant cellular differentiation and development of cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA098699-01
Application #
6569870
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Tricoli, James
Project Start
2003-05-01
Project End
2005-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
1
Fiscal Year
2003
Total Cost
$149,536
Indirect Cost
Name
University of Washington
Department
Urology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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