Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy.
OBJECTIVE
The cancer stem cell (CSC) paradigm hypothesizes that successful clinical eradication of CSCs may lead to durable remission for patients with ovarian cancer. Despite mounting evidence in support of ovarian CSCs, their phenotype and clinical relevance remain unclear. We and others have found high aldehyde dehydrogenase 1 (ALDH(high)) expression in a variety of normal and malignant stem cells, and sought to better characterize ALDH(high) cells in ovarian cancer.


METHODS
We compared ALDH(high) to ALDH(low) cells in two ovarian cancer models representing distinct subtypes: FNAR-C1 cells, derived from a spontaneous rat endometrioid carcinoma, and the human SKOV3 cell line (described as both serous and clear cell subtypes). We assessed these populations for stem cell features then analyzed expression by microarray and qPCR.


RESULTS
ALDH(high) cells displayed CSC properties, including: smaller size, quiescence, regenerating the phenotypic diversity of the cell lines in vitro, lack of contact inhibition, nonadherent growth, multi-drug resistance, and in vivo tumorigenicity. Microarray and qPCR analysis of the expression of markers reported by others to enrich for ovarian CSCs revealed that ALDH(high) cells of both models showed downregulation of CD24, but inconsistent expression of CD44, KIT and CD133. However, the following druggable targets were consistently expressed in the ALDH(high) cells from both models: mTOR signaling, her-2/neu, CD47 and FGF18/FGFR3.


CONCLUSIONS
Based on functional characterization, ALDH(high) ovarian cancer cells represent an ovarian CSC population. Differential gene expression identified druggable targets that have the potential for therapeutic efficacy against ovarian CSCs from multiple subtypes.
['Sharrow|Allison C|AC|', 'Perkins|Brandy|B|', 'Collector|Michael I|MI|', 'Yu|Wayne|W|', 'Simons|Brian W|BW|', 'Jones|Richard J|RJ|']
D000080924:Aldehyde Dehydrogenase 1 Family D000445:Aldehyde Oxidoreductases D000818:Animals D048708:Cell Growth Processes D005260:Female D006801:Humans D058990:Molecular Targeted Therapy D014411:Neoplastic Stem Cells D010051:Ovarian Neoplasms D051381:Rats D011917:Rats, Inbred Lew D050697:Retinal Dehydrogenase
Aldehyde dehydrogenase 1 Ovarian cancer Cancer stem cells Stem cell-targeted therapy