A short-term colorectal cancer sphere culture as a relevant tool for human cancer biology investigation

• Published in: British journal of cancer Vol. 108; no. 8; pp. 1720 - 1731
• Main Authors: Weiswald, L-B, Richon, S, Massonnet, G, Guinebretière, J-M, Vacher, S, Laurendeau, I, Cottu, P, Marangoni, E, Nemati, F, Validire, P, Bellet, D, Bièche, I, Dangles-Marie, V
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.04.2013; Nature Publishing Group
• Subjects: 631/67/70; 692/308; 692/699/67/1504/1885; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Camptothecin - analogs & derivatives; Camptothecin - pharmacology; Cancer Research; Cancer therapies; Cell Line, Tumor; Cell Movement - physiology; Cell Survival - physiology; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Drug Resistance; Drug Screening Assays, Antitumor; Epidemiology; Female; Fluorouracil - pharmacology; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; Humans; Medical sciences; Metastasis; Mice; Mice, Nude; Mice, SCID; Microscopy, Confocal; Molecular Diagnostics; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Transplantation; Oncology; Random Allocation; Real-Time Polymerase Chain Reaction; Spheroids, Cellular - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Transplantation, Heterologous; Tumors; Xenograft Model Antitumor Assays; Canada; France; Vancouver British Columbia Canada; Paris France; colospheres; model; colorectal cancer; three-dimension; Short term; Human; Rectal disease; ex vivo model; Colorectal cancer; Biology; Dimension; Malignant tumor; Colonic disease; Cancerology; Ex vivo; Digestive diseases; Intestinal disease; Models; Cultural aspect; Cancer; Tool
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.132

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. Conclusion: Colospheres closely mimic biological characteristics of in vivo CRC tumours. Consequently, they would be relevant ex vivo CRC models.