Attributes of Oct4 in stem cell biology: Perspectives on cancer stem cells of the ovary

Journal of Ovarian Research (Impact Factor: 2.43). 11/2012; 5(1):37. DOI: 10.1186/1757-2215-5-37
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Epithelial ovarian cancer (EOC) remains the most lethal of all the gynaecological malignancies with drug resistance and recurrence remaining the major therapeutic barrier in the management of the disease. Although several studies have been undertaken to understand the mechanisms responsible for chemoresistance and subsequent recurrence in EOC, the exact mechanisms associated with chemoresistance/recurrence continue to remain elusive. Recent studies have shown that the parallel characteristics commonly seen between embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSC) are also shared by a relatively rare population of cells within tumors that display stem cell-like features. These cells, termed 'cancer initiating cells' or 'cancer stem cells (CSCs)' have been shown not only to display increased self renewal and pluripotent abilities as seen in ESCs and iPSCs, but are also highly tumorigenic in in vivo mouse models. Additionally, these CSCs have been implicated in tumor recurrence and chemoresistance, and when isolated have consistently shown to express the master pluripotency and embryonic stem cell regulating gene Oct4. This article reviews the involvement of Oct4 in cancer progression and chemoresistance, with emphasis on ovarian cancer. Overall, we highlight why ovarian cancer patients, who initially respond to conventional chemotherapy subsequently relapse with recurrent chemoresistant disease that is essentially incurable.

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Available from: Nuzhat Ahmed, Feb 17, 2015

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Article: Attributes of Oct4 in stem cell biology: Perspectives on cancer stem cells of the ovary

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    • "Additionally supporting our thesis about ovarian embryonic stem cells reactivation in SBT and OSC was the expression of Oct-4 embryonic stem cell marker in the early normal ovarian development , as well as in tumorous tissue of SBT and OSC. Our finding of Oct-4 positivity during ovarian embryonic development accords with its pivotal role in the maintenance of self-renewal and pluripotency of embryonic stem cells (Samardzija et al., 2012). Expression of Oct-4 in SBT and OSC reveals the presence of subpopulation of cells which is either dedifferentiated or which silently retained stemness from the period of ovarian developmental. "
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    ABSTRACT: Cell differentiation and different pathways of cell death were immunohistochemically analyzed in ovaries of six human embryos, 20 serous borderline tumors (SBT) and ovarian serous carcinomas (OSC) using markers for apoptosis (caspase-3, AIF, TUNEL) and stemness (Oct-4). In the 5-8-week ovaries, caspase-3 was absent in the ovarian surface epithelium (ose) and mildly positive in the ovarian stroma (os), AIF was expressed moderately, while Oct-4 expression gradually decreased during that period. Some ovarian cells expressed only caspase-3 or AIF together with TUNEL, while both caspase-3 and AIF were co-expressed in other ovarian cells. Mild expression of Oct-4 and caspase-3 characterized some cells of SBT, while their expression varied from mild to strong in OSC. AIF displayed mild to strong expression in ose of SBT and moderate to strong expression in OSC, while no expression of AIF was observed in os of both tumors. In the ose of both SBT and OSC, caspase-3 and AIF were co-expressed only occasionally, while AIF and Oct-4 were co-expressed strongly. Our study showed the presence of stemness cells and different pathways of cell death (caspase-3 and AIF-mediated) in the ovarian tissue during development and carcinogenesis, indicating the correlation between developmental plasticity in human embryonic ovaries and OSC.
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    ABSTRACT: In spite of recent progress in cancer therapeutics and increased knowledge about the cellular and molecular biology of cancer, ovarian cancer still remains a clinical challenge. Chemoresistance followed by tumor recurrence are major causes of poor survival rates of ovarian cancer patients. In recent years, ovarian cancer has been described as a stem cell disease. In this scenario, a small percentage of ovarian tumor cells with cancer stem cell-like properties should survive therapeutic treatments by activating the self-renewal and differentiating pathways resulting in tumor progression and clinical recurrence. The mere concept that a small subset of cells in the tumor population drives tumor formation and recurrence after therapies has major implications for therapeutic development. This review focuses on the current understanding of normal and malignant ovarian stem cells in an attempt to contribute to our understanding the mechanisms responsible for tumor development as well as recurrence after chemotherapy. We also discuss recent findings on the cancer stem cell niche and how tumor and associated cells in the niche may respond to chemotherapeutic stress by activating autocrine and paracrine programs which may opt as survival mechanisms for residual cells in response to frontline chemotherapy. Using mouse ovarian cancer models we highlight the role of cancer stem cells in response to chemotherapy, and relate how cancer stem cells may impact on recurrence. Understanding the distinct mechanisms that facilitate cancer stem cell survival and propagation are likely to reveal opportunities for improving the treat outcomes for ovarian cancer patients.
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