title: Characterization of cervical cancer stem cell-like cells: phenotyping, stemness, and human papilloma virus co-receptor expression.
abstract: Cancer stem cells (CSC) exhibit high tumorigenic capacity in several tumor models. We have now determined an extended phenotype for cervical cancer stem cells. Our results showed increased CK-17, p63+, AII+, CD49f+ expression in these cells, together with higher Aldehyde dehydrogenase (ALDHbright)activity in Cervical CSC (CCSC) enriched in cervospheres. An increase in stem cell markers, represented by OCT-4, Nanog, and β-catenin proteins, was also observed, indicating that under our culture conditions, CCSC are enriched in cervospheres, as compared to monolayer cultures. In addition, we were able to show that an increased ALDHbright activity correlated with higher tumorigenic activity. Flow cytometry and immunflorescence assays demonstrated that CCSC in cervosphere cultures contain a sub-population of cells that contain Annexin II, a Human papillomavirus (HPV) co-receptor. Taken together, under our conditions there is an increase in the number of CCSC in cervosphere cultures which exhibit the following phenotype: CK-17, p63+, AII+, CD49f+ and high ALDH activity, which in turn correlates with higher tumorigenicity. The presence of Annexin II and CD49f in CCSC opens the possibility that normal cervical stem cells could be the initial target of infection by high risk HPV.
authors.affiliation: Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Secretaría de Salud (SS), México City, Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ortiz-Sánchez
authors.affiliation: Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Secretaría de Salud (SS), México City, Mexico.
authors.forename: Luz
authors.initials: L
authors.lastname: Santiago-López
authors.affiliation: Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Secretaría de Salud (SS), México City, Mexico.
authors.forename: Verónica B
authors.initials: VB
authors.lastname: Cruz-Domínguez
authors.affiliation: Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Secretaría de Salud (SS), México City, Mexico.
authors.forename: Mariel E
authors.initials: ME
authors.lastname: Toledo-Guzmán
authors.affiliation: Laboratorio de Marcadores Moleculares, Hospital Infantil de México "Federico Gómez", SA, Mexico City, Mexico.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hernández-Cueto
authors.affiliation: Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Secretaría de Salud (SS), México City, Mexico.
authors.forename: Saé
authors.initials: S
authors.lastname: Muñiz-Hernández
authors.affiliation: Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City, Mexico.
authors.forename: Efraín
authors.initials: E
authors.lastname: Garrido
authors.affiliation: Subdirección de Investigación Clínica, Instituto Nacional de Cancerología, Secretaría de Salud (SS), México City, Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Cantú De León
authors.affiliation: Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM) and Instituto Nacional de Cancerología, Secretaría de Salud (SS), Mexico City, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: García-Carrancá
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D039503:Integrin alpha6 / Q000378:metabolism; D053537:Keratin-17 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D018874:Spheroids, Cellular; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D014408:Biomarkers, Tumor; D039503:Integrin alpha6; D053537:Keratin-17; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000444:Aldehyde Dehydrogenase
keywords: ALDH activity; cervical cancer; cervical cancer stem cell phenotype; cervospheres; stemness markers