Cancer Stem Cells and Aneuploid Populations within Developing Tumors Are the Major Determinants of Tumor Dormancy

被引:142
作者
Kusumbe, Anjali P. [1 ]
Bapat, Sharmila A. [1 ]
机构
[1] Natl Ctr Cell Sci, Pune 411007, Maharashtra, India
关键词
OVARIAN-CANCER; PROSPECTIVE IDENTIFICATION; INITIATING CELLS; SELF-RENEWAL; IN-VIVO; PROLIFERATION; APOPTOSIS; CD133(+); IMMORTALIZATION; TUMORIGENESIS;
D O I
10.1158/0008-5472.CAN-09-2802
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tumor formation involves substantial cell division and genetic instability, but the relationship between quiescent cancer stein cells (CSC) and dividing progenitors in these events is poorly understood. Likewise, the implication of aneuploid cells in solid tumors is uncertain. CSCs are postulated to contribute to tumor dormancy and present a formidable obstacle in limiting treatment outcomes for a majority of cancers, whereas the genetic heterogeneity conjured by aneuploid cells may influence tumor drug resistance. However, direct confirmation of these events remains forthcoming. lit the present study, we addressed the identification of tumor dormancy in terms of isolation of therapy-refractory residual tumor cells from tumors that persist in a state of quiescence as label-retaining cells. The choices of label were PKH67/PKH26 dyes that irreversibly bind to the lipid bilayer on cell membranes and get equally partitioned among daughter cells subsequent. to each cell division. Consequent characterization revealed that label-retaining cells encompass two different populations capable of remaining in a state of quiescence, i.e., stern-like cells and aneuploid cells. The former express a reversibility of quiescence through retention of functionality and also exhibit therapeutic refractoriness; the latter seem to be either quiescent or proliferation-arrested at steady-state. Subsequent to exposure to selective pressure of chemotherapy, a fraction of these cells may acquire the potential to proliferate in a drug-refractory manner and acquire stem-like characteristics. Collectively, the findings of the present study reveal that tumor-derived CSCs and aneuploid populations contribute to drug resistance and tumor dormancy in cancer progression. [Cancer Res 2009:69(24):9245-53]
引用
收藏
页码:9245 / 9253
页数:9
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