title: Extensive characterization of sphere models established from colorectal cancer cell lines.
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 copy-number. 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.
authors.affiliation: Inserm, UMRS_938, Centre de Recherche Saint-Antoine, Equipe "Instabilité des Microsatellites et Cancers", 75012, Paris, France. ada.collura@inserm.fr
authors.forename: Ada
authors.initials: A
authors.lastname: Collura
authors.forename: Laetitia
authors.initials: L
authors.lastname: Marisa
authors.forename: Diletta
authors.initials: D
authors.lastname: Trojan
authors.forename: Olivier
authors.initials: O
authors.lastname: Buhard
authors.forename: Anaïs
authors.initials: A
authors.lastname: Lagrange
authors.forename: Arnaud
authors.initials: A
authors.lastname: Saget
authors.forename: Marianne
authors.initials: M
authors.lastname: Bombled
authors.forename: Patricia
authors.initials: P
authors.lastname: Méchighel
authors.forename: Mira
authors.initials: M
authors.lastname: Ayadi
authors.forename: Martine
authors.initials: M
authors.lastname: Muleris
authors.forename: Aurélien
authors.initials: A
authors.lastname: de Reynies
authors.forename: Magali
authors.initials: M
authors.lastname: Svrcek
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Fléjou
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Florent
authors.forename: Florence
authors.initials: F
authors.lastname: Mahuteau-Betzer
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Faussat
authors.forename: Alex
authors.initials: A
authors.lastname: Duval
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local; D012007:Rectum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D005472:Fluorouracil