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Identification of a distinct population of CD133(+)CXCR4(+) cancer stem cells in ovarian cancer.

TitleIdentification of a distinct population of CD133(+)CXCR4(+) cancer stem cells in ovarian cancer.
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2015
AuthorsCioffi, Michele, D'Alterio Crescenzo, Camerlingo Rosalba, Tirino Virginia, Consales Claudia, Riccio Anna, Ieranò Caterina, Cecere Sabrina Chiara, Losito Nunzia Simona, Greggi Stefano, Pignata Sandro, Pirozzi Giuseppe, and Scala Stefania
JournalSci Rep
Volume5
Pagination10357
Date Published2015 May 28
ISSN20452322
KeywordsAC133 Antigen, Animals, Antigens, CD, cell lineage, cisplatin, Drug Resistance, Neoplasm, Female, Glycoproteins, HCT116 Cells, Humans, Mice, Neoplastic Stem Cells, Ovarian Neoplasms, Peptides, Receptors, CXCR4
Abstract

CD133 and CXCR4 were evaluated in the NCI-60 cell lines to identify cancer stem cell rich populations. Screening revealed that, ovarian OVCAR-3, -4 and -5 and colon cancer HT-29, HCT-116 and SW620 over expressed both proteins. We aimed to isolate cells with stem cell features sorting the cells expressing CXCR4(+)CD133(+) within ovarian cancer cell lines. The sorted population CD133(+)CXCR4(+) demonstrated the highest efficiency in sphere formation in OVCAR-3, OVCAR-4 and OVCAR-5 cells. Moreover OCT4, SOX2, KLF4 and NANOG were highly expressed in CD133(+)CXCR4(+) sorted OVCAR-5 cells. Most strikingly CXCR4(+)CD133(+) sorted OVCAR-5 and -4 cells formed the highest number of tumors when inoculated in nude mice compared to CD133(-)CXCR4(-), CD133(+)CXCR4(-), CD133(-)CXCR4(+) cells. CXCR4(+)CD133(+) OVCAR-5 cells were resistant to cisplatin, overexpressed the ABCG2 surface drug transporter and migrated toward the CXCR4 ligand, CXCL12. Moreover, when human ovarian cancer cells were isolated from 37 primary ovarian cancer, an extremely variable level of CXCR4 and CD133 expression was detected. Thus, in human ovarian cancer cells CXCR4 and CD133 expression identified a discrete population with stem cell properties that regulated tumor development and chemo resistance. This cell population represents a potential therapeutic target.

DOI10.1038/srep10357
Alternate JournalSci Rep
Citation Key6756
PubMed ID26020117
PubMed Central IDPMC4650662