title: Identification of a distinct population of CD133(+)CXCR4(+) cancer stem cells in ovarian cancer.
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.
authors.affiliation: Molecular Immunology and Immuneregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" IRCCS-ITALIA. Via Mariano Semmola 80131, Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cioffi
authors.affiliation: Molecular Immunology and Immuneregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" IRCCS-ITALIA. Via Mariano Semmola 80131, Naples, Italy.
authors.forename: Crescenzo
authors.initials: C
authors.lastname: D'Alterio
authors.affiliation: Stem Cell Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" IRCCS-ITALIA. Via Mariano Semmola 80131, Naples, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Camerlingo
authors.affiliation: Stem Cell Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" IRCCS-ITALIA. Via Mariano Semmola 80131, Naples, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Tirino
authors.affiliation: Molecular Immunology and Immuneregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" IRCCS-ITALIA. Via Mariano Semmola 80131, Naples, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Consales
authors.affiliation: Molecular Immunology and Immuneregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" IRCCS-ITALIA. Via Mariano Semmola 80131, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Riccio
authors.affiliation: Molecular Immunology and Immuneregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" IRCCS-ITALIA. Via Mariano Semmola 80131, Naples, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Ieranò
authors.affiliation: Uro-Gynecological Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" IRCCS-ITALIA. Via Mariano Semmola 80131, Naples, Italy.
authors.forename: Sabrina Chiara
authors.initials: SC
authors.lastname: Cecere
authors.affiliation: Pathology; Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" IRCCS-ITALIA. Via Mariano Semmola 80131, Naples, Italy.
authors.forename: Nunzia Simona
authors.initials: NS
authors.lastname: Losito
authors.affiliation: Uro-Gynecological Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" IRCCS-ITALIA. Via Mariano Semmola 80131, Naples, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Greggi
authors.affiliation: Uro-Gynecological Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" IRCCS-ITALIA. Via Mariano Semmola 80131, Naples, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Pignata
authors.affiliation: Stem Cell Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" IRCCS-ITALIA. Via Mariano Semmola 80131, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pirozzi
authors.affiliation: Molecular Immunology and Immuneregulation, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" IRCCS-ITALIA. Via Mariano Semmola 80131, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Scala
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010455:Peptides / Q000235:genetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C527276:CXCR4 protein, human; D006023:Glycoproteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D019718:Receptors, CXCR4; D002945:Cisplatin