Extensive characterization of sphere models established from colorectal cancer cell lines
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Cellular and Molecular Life Sciences
RESEARCH ARTICLE
Extensive characterization of sphere models established from colorectal cancer cell lines Ada Collura • Laetitia Marisa • Diletta Trojan • Olivier Buhard • Anaı¨s Lagrange • Arnaud Saget • Marianne Bombled • Patricia Me´chighel Mira Ayadi • Martine Muleris • Aure´lien de Reynies • Magali Svrcek • Jean-Franc¸ois Fle´jou • Jean-Claude Florent • Florence Mahuteau-Betzer • Anne-Marie Faussat • Alex Duval
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Received: 27 May 2012 / Revised: 3 September 2012 / Accepted: 4 September 2012 / Published online: 25 September 2012 Ó Springer Basel AG 2012
Abstract Links between cancer and stem cells have been proposed for many years. As the cancer stem cell (CSC) theory became widely studied, new methods were developed to culture and expand cancer cells with conserved determinants of ‘‘stemness’’. These cells show increased ability to grow in suspension as spheres in serum-free medium supplemented with growth factors and chemicals. The physiological relevance of this phenomenon in established cancer cell lines remains unclear. Cell lines have traditionally been used to explore tumor biology and serve as preclinical models for the screening of potential therapeutic agents. Here, we grew cell-forming spheres (CFS) from 25 established colorectal cancer cell lines. The molecular and cellular characteristics of CFS were compared to the bulk of tumor cells. CFS could be isolated from 72 % of the cell lines. Both CFS and their parental
CRC cell lines were highly tumorigenic. Compared to their parental cells, they showed similar expression of putative CSC markers. The ability of CRC cells to grow as CFS was greatly enhanced by prior treatment with 5-fluorouracil. At the molecular level, CFS and parental CRC cells showed identical gene mutations and very similar genomic profiles, although microarray analysis revealed changes in CFS gene expression that were independent of DNA copynumber. We identified a CFS gene expression signature common to CFS from all CRC cell lines, which was predictive of disease relapse in CRC patients. In conclusion, CFS models derived from CRC cell lines possess interesting phenotypic features that may have clinical relevance for drug resistance and disease relapse. Keywords Colorectal cancer Colon cancer cell lines Spheres Microarray
Electronic supplementary material The online version of this article (doi:10.1007/s00018-012-1160-9) contains supplementary material, which is available to authorized users. A. Collura D. Trojan O. Buhard A. Lagrange A. Saget P. Me´chighel M. Muleris M. Svrcek J.-F. Fle´jou A. Duval Inserm, UMRS_938, Centre de Recherche Saint-Antoine, Equipe ‘‘Instabilite´ des Microsatellites et Cancers’’, 75012 Paris, France A. Collura D. Trojan O. Buhard A. Lagrange A. Saget P. Me´chighel M. Muleris M. Svrcek J.-F. Fle´jou A.-M. Faussat A. Duval Universite´ Pierre et Marie Curie-Paris6, Paris, France L. Marisa M. Ayadi A. de Reynies Programme ‘‘Cartes d’Identite´ des Tumeurs’’, Ligue Nationa
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