Abstract
Tumor formation and growth is dictated by a very small number of tumor cells, called cancer stem cells, which are capable of self-renewal. The genesis of cancer stem cells and their resistance to conventional chemotherapy and radiotherapy via mechanisms such as multidrug resistance, quiescence, enhanced DNA repair abilities and anti-apoptotic mechanisms, make it imperative to develop methods to identify and use these cells as diagnostic or therapeutic targets. Aldehyde dehydrogenase 1 (ALDH1) is used as a cancer stem cell marker. In this study, we evaluated ALDH1 expression in CaSki, HeLa and SiHa cervical cancer cells using the Aldefluor method to isolate ALDH1-positive cells. We showed that higher ALDH1 expression correlated with significantly higher rates of cell proliferation, microsphere formation and migration. We also could demonstrate that SiHa-ALDH1- positive cells were significantly more tumorigenic compared to SiHa-ALDH1-negative cells. Similarly, SiHa cells overexpressing ALDH1 were significantly more tumorigenic and showed higher rates of cell proliferation and migration compared to SiHa cells where ALDH1 expression was knocked down using a lentivirus vector. Our data suggested that ALDH1 is a marker of cervical cancer stem cells and expand our understanding of its functional role.
Highlights
Cervical cancer is the most commonly occurring cancer of the female reproductive tract (Stanley, 2010)
We evaluated Aldehyde dehydrogenase 1 (ALDH1) expression in cervical cancer cells and showed that ALDH1-positive cells exhibited the properties of cancer stem cells
We investigated the role of ALDH1 in tumorigenesis and metastasis of three different cervical carcinoma cell lines
Summary
Cervical cancer is the most commonly occurring cancer of the female reproductive tract (Stanley, 2010). Tumor recurrence after conventional therapy has been suggested to be due to the presence of these slow-cycling, cancer stem cells, which are capable of initiating and sustaining neoplastic growth (Sagar et al, 2007; Ghaffari, 2011). Dysregulation of key signaling pathways such as the Wnt, Hedgehog, Notch and TGF-β/BMP pathways plays an important role in modulating tumorigenesis as well as stem cell function, suggesting that tumors may originate from transformed normal stem cells (Logan and Nusse, 2004). These studies suggest that identification and targeting of cancer stem cells are key aspects to optimizing cancer therapy
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