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Molecular Biology Reports

, Volume 41, Issue 4, pp 1993–2004 | Cite as

Side populations from cervical-cancer-derived cell lines have stem-cell-like properties

  • Jairo Villanueva-Toledo
  • Alberto Ponciano-Gómez
  • Elizabeth Ortiz-Sánchez
  • Efraín GarridoEmail author
Article

Abstract

The target cells for the transforming mutations caused by high-risk human papillomavirus (HPV) infection could be the stem cells of the uterine cervical epithelium, generating particular cancer stem cells (CSCs). The aim of this study was to identify and characterize the CSCs from cervical-cancer-derived cell lines. The ability of SiHa, CaLo, and C-33A cell lines to efflux Hoechst 33342 was evaluated by flow cytometry and cells from the corresponding side populations (SPs) and nonside populations (NSPs) were analyzed for their cell-cycle status (pyronin Y) and their mRNA levels of ABC transporter family members (with qPCR). Specific markers (α6-integrinbri/CD71dim, CK17) of normal epithelial stem cells were evaluated by flow cytometry. The biological properties of these cells were analyzed, including their colony heterogeneity, repopulation, and anchorage-independent colony formation. We identified SPs (around 3 %) in the SiHa and CaLo cell lines, more than 70 % of which were in G0 phase and strongly expressed ABC transporters (predominantly ABCG2 and ABCB1). The SP from CaLo cells showed an α6-integrinbri/CDdim pattern, whereas the SP from the SiHa cells showed an α6-integrin/CDdim pattern. Recultured cells from the SPs of both cell lines generated both SPs and NSPs, and had higher clonogenic potential to form mainly holoclones and greater colony-forming efficiency under anchorage-independent growth conditions than the cells from the NSPs or total cell populations. Interestingly, we identified no SP in the HPV-uninfected C-33A cell line, and it did not express ABCG2 or other members of the ABC transporters (ABCB1, ABCC1, or ABCA3).

Keywords

Cancer stem cells Side population Cervical cancer ABC transporters Hoechst 33342 

Abbreviations

SP

Side population

NSP

Nonside population

CSCs

Cancer stem cells

RNA

Ribonucleic acid

HPV

Human papillomavirus

DMEM

Dulbecco’s modified Eagle’s medium

F12

Nutrient mixture F12

FITC

Fluorescein isothiocyanate

HEK293

Human embryonic kidney 293 cells

FBS

Fetal bovine serum

PE

Phycoerythrin

PY

Pyronin Y

qPCR

Quantitative polymerase chain reaction

RT-qPCR

Reverse transcription-quantitative PCR

ΔΔCt

Double delta Ct

Notes

Acknowledgments

We gratefully acknowledge Pedro Chavez for his helpful technical assistance and Victor Rosales for his technical support with the cell sorting techniques and data analysis. This work was supported by a grant from CONACyT (Project No. 105174). JVT received a scholarship from CONACyT (173031).

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Jairo Villanueva-Toledo
    • 1
  • Alberto Ponciano-Gómez
    • 1
  • Elizabeth Ortiz-Sánchez
    • 2
  • Efraín Garrido
    • 1
    Email author
  1. 1.Laboratory of Research in Cancer Molecular and Cell Biology, Departamento de Genética y Biología MolecularCINVESTAV-IPNMexicoMexico
  2. 2.Unidad de Investigación Biomédica en Cáncer, División de Investigación Básica, Instituto Nacional de CancerologíaSecretaría de SaludMexicoMexico

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