Ovarian carcinoma tumor-initiating cells have a mesenchymal phenotype

Francesca Ricci, Sergio Bernasconi, Patrizia Perego, Monica Ganzinelli, Giorgio Russo, Francesca Bono, Costantino Mangioni, Robert Fruscio, Mauro Signorelli, Massimo Broggini, Giovanna Damia

Research output: Contribution to journalArticle

Abstract

Solid tumors appear to contain a subpopulation of cells (tumor-initiating cells, TICs) that not only drives and sustains tumor growth, but is possibly responsible for recurrence. We isolated, after enzymatic digestion of primary ovarian carcinoma samples, a subpopulation of cells propagating as non-adherent spheres in medium suitable for tumor stem cells. These cells were able to self-renew in vitro, as suggested by PKH-26 staining studies, were tumorigenic and acquired an epithelial morphology when grown in FBS-supplemented medium, losing their tumorigenic potential. Interestingly, the tumorigenic potential of PKH-26high- and PKH-26neg-sorted cells was similar. These TIC-enriched cultures showed higher levels of genes involved in stemness than differentiated cells derived from them and were more resistant to the cytotoxic effects of some drugs but equally sensitive to others. The higher level of ABCG2 efflux pump could explain increased resistance to taxol and VP16, and higher levels of genes involved in nucleotide excision repair partially explain the resistance to cisplatin. These cells express mesenchymal markers and epithelial transition could be induced when cultured in differentiating conditions, with a loss of invasive potential. These data suggest that ovarian cancer is a stem cell disease and should help elucidate the role of these cells in the aggressive phenotype of this tumor and find new therapeutic strategies to reduce resistance to current chemotherapeutic drugs.

Original languageEnglish
Pages (from-to)1966-1976
Number of pages11
JournalCell Cycle
Volume11
Issue number10
DOIs
Publication statusPublished - May 15 2012

Fingerprint

Neoplastic Stem Cells
Carcinoma
Phenotype
Neoplasms
Epithelial-Mesenchymal Transition
Paclitaxel
DNA Repair
Pharmaceutical Preparations
Ovarian Neoplasms
Cisplatin
Genes
Digestion
Stem Cells
Cell Culture Techniques
Staining and Labeling
Recurrence
Growth

Keywords

  • Anticancer agents
  • Mesenchymal phenotype
  • Ovarian tumor
  • PKH26
  • Tumor-initiating cell

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Ricci, F., Bernasconi, S., Perego, P., Ganzinelli, M., Russo, G., Bono, F., ... Damia, G. (2012). Ovarian carcinoma tumor-initiating cells have a mesenchymal phenotype. Cell Cycle, 11(10), 1966-1976. https://doi.org/10.4161/cc.20308

Ovarian carcinoma tumor-initiating cells have a mesenchymal phenotype. / Ricci, Francesca; Bernasconi, Sergio; Perego, Patrizia; Ganzinelli, Monica; Russo, Giorgio; Bono, Francesca; Mangioni, Costantino; Fruscio, Robert; Signorelli, Mauro; Broggini, Massimo; Damia, Giovanna.

In: Cell Cycle, Vol. 11, No. 10, 15.05.2012, p. 1966-1976.

Research output: Contribution to journalArticle

Ricci, F, Bernasconi, S, Perego, P, Ganzinelli, M, Russo, G, Bono, F, Mangioni, C, Fruscio, R, Signorelli, M, Broggini, M & Damia, G 2012, 'Ovarian carcinoma tumor-initiating cells have a mesenchymal phenotype', Cell Cycle, vol. 11, no. 10, pp. 1966-1976. https://doi.org/10.4161/cc.20308
Ricci F, Bernasconi S, Perego P, Ganzinelli M, Russo G, Bono F et al. Ovarian carcinoma tumor-initiating cells have a mesenchymal phenotype. Cell Cycle. 2012 May 15;11(10):1966-1976. https://doi.org/10.4161/cc.20308
Ricci, Francesca ; Bernasconi, Sergio ; Perego, Patrizia ; Ganzinelli, Monica ; Russo, Giorgio ; Bono, Francesca ; Mangioni, Costantino ; Fruscio, Robert ; Signorelli, Mauro ; Broggini, Massimo ; Damia, Giovanna. / Ovarian carcinoma tumor-initiating cells have a mesenchymal phenotype. In: Cell Cycle. 2012 ; Vol. 11, No. 10. pp. 1966-1976.
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