Developing ovarian cancer stem cell models: laying the pipeline from discovery to clinical intervention

被引:55
作者
Ffrench, Brendan [1 ,2 ]
Gasch, Claudia [1 ,2 ]
O'Leary, John J. [1 ,2 ]
Gallagher, Michael F. [1 ,2 ]
机构
[1] St James Hosp, Dept Histopathol, Trinity Coll Dublin, Trinity Ctr Hlth Sci, Dublin 8, Ireland
[2] Coombe Womens & Infants Univ Hosp, Pathol Dept, Dublin 8, Ireland
关键词
Ovarian cancer; Cancer stem cells; Stem cell models; Proliferate to kill; Clonal cancer stemness; Aldehyde dehydrogenase; Hoechst; Cluster of differentiation (CD) proteins; EPIDERMAL-GROWTH-FACTOR; SIDE-POPULATION CELLS; ALDEHYDE DEHYDROGENASE; PROSPECTIVE IDENTIFICATION; SURFACE EPITHELIUM; SELF-RENEWAL; TUMOR-GROWTH; EXPRESSION; CD133; CD44;
D O I
10.1186/1476-4598-13-262
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Despite decades of research, ovarian cancer is still associated with unacceptably high mortality rates, which must be addressed by novel therapeutic approaches. One avenue through which this may be achieved is targeting of tumor-initiating 'Cancer Stem Cells' (CSCs). CSCs are sufficient to generate primary and recurrent disease through extensive rounds of asymmetric division, which maintain the CSC pool while producing the tissues that form the bulk of the tumor. CSCs thrive in the harsh tumor niche, are generally refractory to therapeutic intervention and closely-linked to the Epithelial-Mesenchymal Transition process, which facilitates invasion and metastasis. While it is well-accepted that CSC-targeting must be assessed as a novel therapeutic avenue, few ovarian CSC models have been developed due to perceived and actual difficulties associated with the process of 'CSC Discovery'. In this article we review contemporary approaches to CSC Discovery and argue that this process should start with an understanding of the specific challenges associated with clinical intervention, laying the pipeline backwards towards CSC Discovery. Such an approach would expedite the bridging of the gap between laboratory isolation and clinical targeting of ovarian CSCs.
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页数:15
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