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Review
. 2013 Mar 25;14(4):6624-48.
doi: 10.3390/ijms14046624.

V体育官网 - Regulation of ovarian cancer stem cells or tumor-initiating cells

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Review

"V体育ios版" Regulation of ovarian cancer stem cells or tumor-initiating cells

Mi Jeong Kwon (VSports) et al. Int J Mol Sci. .

VSports注册入口 - Abstract

Cancer stem cells or tumor-initiating cells (CSC/TICs), which can undergo self-renewal and differentiation, are thought to play critical roles in tumorigenesis, therapy resistance, tumor recurrence and metastasis. Tumor recurrence and chemoresistance are major causes of poor survival rates of ovarian cancer patients, which may be due in part to the existence of CSC/TICs. Therefore, elucidating the molecular mechanisms responsible for the ovarian CSC/TICs is required to develop a cure for this malignancy. Recent studies have indicated that the properties of CSC/TICs can be regulated by microRNAs, genes and signaling pathways which also function in normal stem cells. Moreover, emerging evidence suggests that the tumor microenvironments surrounding CSC/TICs are crucial for the maintenance of these cells. Similarly, efforts are now being made to unravel the mechanism involved in the regulation of ovarian CSC/TICs, although much work is still needed. This review considers recent advances in identifying the genes and pathways involved in the regulation of ovarian CSC/TICs. Furthermore, current approaches targeting ovarian CSC/TICs are described VSports手机版. Targeting both CSC/TICs and bulk tumor cells is suggested as a more effective approach to eliminating ovarian tumors. Better understanding of the regulation of ovarian CSC/TICs might facilitate the development of improved therapeutic strategies for recurrent ovarian cancer. .

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"V体育官网入口" Figures

Figure 1
Figure 1
The tumor microenvironment involved in the maintenance and regulation of ovarian CSC/TICs. The maintenance and properties of the ovarian CSC/TIC population are influenced by the surrounding microenvironment, termed the “CSC/TIC niche.” Growth factors, such as bone morphogenetic protein (BMP) and transforming growth factor-β (TGF-β) released from ovarian cancer cells, increase the self-renewal and proliferation of CSC/TICs. Ovarian carcinoma associated-mesenchymal stem cells (CA-MSCs) are also reported to regulate ovarian CSC/TICs through BMP signaling. Moreover, hypoxia, which is a common feature of the ovarian cancer microenvironment, enhances the survival and chemoresistance of ovarian CSC/TICs through the upregulation of c-kit mediated by HIF-1α. Conversely, hypoxic induction of HIF-1 expression can promote the differentiation of ovarian CSC/TICs by inducing TWIST1 expression. A high level of NF-κB activity in ovarian CSC/TICs may be induced by cytokines, such as TNF-α, that are generated as a result of inflammation in the ovarian tumor microenvironment.
Figure 2
Figure 2
Strategies for the effective treatment of recurrent ovarian cancer. (A) Therapeutic strategy to target ovarian CSC/TICs. Therapy targeting ovarian CSC/TICs might eliminate this population from the bulk tumor. However, current studies suggest that differentiated non-CSC/TICs can dedifferentiate into CSC/TICs by EMT or in response to signals from the tumor microenvironment. Therefore, despite initial eradication of the CSC/TIC population, tumor relapse might occur due to the generation of CSC/TICs from the remaining non-CSC/TICs; (B) Therapy targeting ovarian non-CSC/TICs and conventional chemotherapy. Conventional cytotoxic chemotherapy and therapies that do not target ovarian CSC/TICs kill most tumor cells but do not remove CSC/TICs from the bulk tumor. Therefore, the tumor initially shrinks but then grows back due to the remaining CSC/TICs; (C) Combination therapy targeting both ovarian CSC/TICs and bulk tumor cells. Combination treatment of conventional cytotoxic drugs and other drugs that target ovarian CSC/TICs will lead to tumor degeneration through the complete eradication of CSC/TICs. This therapeutic strategy is postulated to prevent tumor recurrence and allow ovarian cancer to be cured.

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