Characterization of cervical cancer stem cell-like cells: phenotyping, stemness, and human papilloma virus co-receptor expression
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Elizabeth Ortiz-Sánchez1, Luz Santiago-López1, Verónica B. Cruz-Domínguez1, Mariel E. Toledo-Guzmán1, Daniel Hernández-Cueto2, Saé Muñiz-Hernández1, Efraín Garrido3, David Cantú De León4 and Alejandro García-Carrancá5
1 Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Secretaría de Salud (SS), México City, Mexico
2 Laboratorio de Marcadores Moleculares, Hospital Infantil de México “Federico Gómez”, SA, Mexico City, Mexico
3 Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City, Mexico
4 Subdirección de Investigación Clínica, Instituto Nacional de Cancerología, Secretaría de Salud (SS), México City, Mexico
5 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
Elizabeth Ortiz-Sánchez, email:
Alejandro García-Carrancá, email:
Keywords: cervical cancer, cervospheres, cervical cancer stem cell phenotype, stemness markers, ALDH activity
Received: September 23, 2015 Accepted: March 06, 2016 Published: March 20, 2016
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.
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