title: A short-term colorectal cancer sphere culture as a relevant tool for human cancer biology investigation.
abstract: BACKGROUND
  Ex vivo colospheres have been previously characterised as a colorectal cancer (CRC) well-rounded multicellular model, exclusively formed by carcinoma cells, and derived from fresh CRC tissue after mechanical dissociation. The ability to form colospheres was correlated with tumour aggressiveness. Their three-dimensional conformation prompted us to further investigate their potential interest as a preclinical cancer tool.
  
  
  METHODS
  Patient-derived CRC xenografts were used to produce numerous colospheres. Mechanism of formation was elucidated by confocal microscopy. Expression analysis of a panel of 64 selected cancer-related genes by real-time qRT-PCR and hierarchical clustering allowed comparison of colospheres with parent xenografts. In vitro and in vivo assays were performed for migration and chemosensitivity studies.
  
  
  RESULTS
  Colospheres, formed by tissue remodelling and compaction, remained viable several weeks in floating conditions, escaping anoikis through their strong cell-cell interactions. Colospheres matched the gene expression profile of the parent xenograft tissue. Colosphere-forming cells migrated in collagen I matrix and metastasised when subrenally implanted in nude mice. Besides, the colosphere responses to 5-fluorouracil and irinotecan, two standard drugs in CRC, reproduced those of the in vivo original xenografts.
  
  
  CONCLUSIONS
  Colospheres closely mimic biological characteristics of in vivo CRC tumours. Consequently, they would be relevant ex vivo CRC models.
authors.affiliation: IFR71 Sciences du Médicament, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Sorbonne Paris Cité, 4 Avenue de l'Observatoire, F-75006 Paris, France.
authors.forename: L-B
authors.initials: LB
authors.lastname: Weiswald
authors.forename: S
authors.initials: S
authors.lastname: Richon
authors.forename: G
authors.initials: G
authors.lastname: Massonnet
authors.forename: J-M
authors.initials: JM
authors.lastname: Guinebretière
authors.forename: S
authors.initials: S
authors.lastname: Vacher
authors.forename: I
authors.initials: I
authors.lastname: Laurendeau
authors.forename: P
authors.initials: P
authors.lastname: Cottu
authors.forename: E
authors.initials: E
authors.lastname: Marangoni
authors.forename: F
authors.initials: F
authors.lastname: Nemati
authors.forename: P
authors.initials: P
authors.lastname: Validire
authors.forename: D
authors.initials: D
authors.lastname: Bellet
authors.forename: I
authors.initials: I
authors.lastname: Bièche
authors.forename: V
authors.initials: V
authors.lastname: Dangles-Marie
mesh_terms: D000818:Animals; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000473:pathology; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin
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