期刊
MOLECULAR MEDICINE
卷 18, 期 8, 页码 1197-1208出版社
SPRINGER
DOI: 10.2119/molmed.2012.00075
关键词
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资金
- National Basic Research Program of China [2011CB910404]
- National Natural Science Foundation of China [81070399]
- Program for New Century Excellent Talents in University [NCET-09-0307]
- Foundation from Science and Technology Commission of Shanghai Municipality [11JC1401501]
Ovarian cancers are heterogeneous and contain stemlike cells that are able to self-renew and are responsible for sustained tumor growth. Metastasis in the peritoneal cavity occurs more frequently in ovarian cancer than in other malignancies, but the underlying mechanism remains largely unknown. We have identified that ovarian cancer stemlike cells (CSCs), which were defined as side population (SP) cells, were present in patients' ascitic fluid and mesenchymally transformed cell lines, ES-2 and HO-8910PM. SP cells, which were sorted from both cell lines and implanted into immunocompromised mice, were localized to the xenografted tumor boundary. In addition, SP cells exhibited an epithelial phenotype and showed a distinct gene expression profile with reduced expression of cell adhesion molecules (CAMS), indicating that SP cells exert an important role in ovarian cancer progression on the basis of their delicate interaction with the surrounding microenvironment and anatomical localization in tumors. In contrast, non-SP cells exhibited a more mesenchymal phenotype and showed more increased invasive potential than SP cells. This heterogeneity was observed as an endogenous transformation via the epithelial-mesenchymal transition (EMT) process, Inhibition of the EMT process by Snail1 silencing reduced the SP cell frequency, and affected their invasive capacity and engraftment. These findings illustrate the interplay between epithelial ovarian CSCs and the EMT, and exert a link to explain tumor heterogeneity and its necessity for ovarian cancer maintenance, metastasis and progression. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00075
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