Characterization of ALDH 1 high ovarian cancer cells: Towards targeted stem cell therapy

abstract

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:

.....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.