Ovarian Carcinoma Stem Cells
Final rept. 15 Apr 2008-14 Apr 2009
JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
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Ovarian carcinoma is one of the most responsive solid tumors, with the majority of affected women now achieving complete remissions unfortunately, most of these women eventually relapse and die from the disease. We hypothesized that the initial clinical responses represent therapeutic effectiveness against differentiated cancer cells making up the bulk of the tumor, while the high rate of relapses result from rare, biologically distinct resistant cancer stem cells CSC. The limited understanding about the phenotype of normal ovarian epithelial stem cells is an obstacle to identifying ovarian CSC, if they exist. However, several characteristics that appear to be shared by normal stem cells from many tissues may serve as markers for CSC from many malignancies. We have developed one of the first true animal models of ovarian cancer, FNAR, a primary rat ovarian cancer that arose spontaneously submitted for publication. FNAR parallels the human disease both biologically expresses Her2neu, estrogen receptors ER and androgen receptors PR and clinically. The pan-stem cell marker ALDH expression appears to identify a CSC subpopulation from the FNAR cells, as the 2-4 of the cells expressing high levels of ALDH are enriched for both in vitro and in vivo clonogenic potential.
- Medicine and Medical Research