Isolation and Characterization of Prostate Cancer Stem Cells
Annual summary 1 Aug 2008-31 Jul 2013
CALIFORNIA UNIV LOS ANGELES
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The aims of this proposal are based on the observations from our initial studies with human prostate cancer surgical specimens. We discovered that prostate stemearly progenitor cells recovered from tumor specimens lack the TMPRSS-ERG translocation found in the original tumor, when examined by fluorescence in situ hybridization FISH. Our findings suggest either ETS rearrangements are not present at the stemprogenitor cell level, or that genetically deranged prostate stemprogenitor cells are particularly vulnerable to apoptosis or senescence in vitro, resulting in selective advantage of benign cells. We have evaluated the growth requirements that enable survival and expansion of prostate stemprogenitor cells from benign and malignant human tissue specimens. As such, we have generated an extensive biorepository of human prostate tissue andor primary cell lines from more than 500 prostate cancer cases that may serve as provide valuable biological tools for understanding the mechanisms of tumorigenesis and identifying new therapeutic targets in future studies. Factors that have affected the ability to isolate and expand primary tumors include low tumor gradevolume present in surgical samples, increased sensitivity of tumor cells to apoptosis after tissue dissociation, semi-competent immune systems in many SCID mouse strains that inhibit tumor take, and a microenvironment that lacks critical growth factors and cellular interactions.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research