A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate cancer derived cell line demonstrating distinct stem-like characteristics

被引:43
作者
Harner-Foreman, Naomi [1 ,2 ]
Vadakekolathu, Jayakumar [1 ]
Laversin, Stephanie A. [1 ,3 ]
Mathieu, Morgan G. [1 ,4 ]
Reeder, Stephen [1 ]
Pockley, A. Graham [1 ]
Rees, Robert C. [1 ]
Boocock, David J. [1 ]
机构
[1] Nottingham Trent Univ, John van Geest Canc Res Ctr, Nottingham NG11 8NS, England
[2] STEMCELL Technol, Bldg 7100,Res Pk,Beach Dr, Cambridge CB25 9TL, England
[3] Univ Southampton, Southampton Gen Hosp, Antibody & Vaccine Grp, Canc Sci Unit,Fac Med, Southampton SO16 6YD, Hants, England
[4] Enzo Life Sci, Ind Str 17, CH-4415 Lausen, Switzerland
关键词
ALDEHYDE DEHYDROGENASE 1; PROSPECTIVE IDENTIFICATION; IN-VITRO; RESISTANCE; EXPRESSION; GROWTH; NANOG; DIFFERENTIATION; PACLITAXEL; PREDICTOR;
D O I
10.1038/srep40633
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cells acquire the invasive and migratory properties necessary for the invasion-metastasis cascade and the establishment of aggressive, metastatic disease by reactivating a latent embryonic programme: epithelial-to-mesenchymal transition (EMT). Herein, we report the development of a new, spontaneous model of EMT which involves four phenotypically distinct clones derived from a primary tumour-derived human prostate cancer cell line (OPCT-1), and its use to explore relationships between EMT and the generation of cancer stem cells (CSCs) in prostate cancer. Expression of epithelial (E-cadherin) and mesenchymal markers (vimentin, fibronectin) revealed that two of the four clones were incapable of spontaneously activating EMT, whereas the others contained large populations of EMT-derived, vimentin-positive cells having spindle-like morphology. One of the two EMT-positive clones exhibited aggressive and stem cell-like characteristics, whereas the other was non-aggressive and showed no stem cell phenotype. One of the two EMT-negative clones exhibited aggressive stem cell-like properties, whereas the other was the least aggressive of all clones. These findings demonstrate the existence of distinct, aggressive CSC-like populations in prostate cancer, but, importantly, that not all cells having a potential for EMT exhibit stem cell-like properties. This unique model can be used to further interrogate the biology of EMT in prostate cancer.
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页数:18
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