Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture
Autor: | Elsa Bayet, Sophie Bravo, Jean-François Bourgaux, Lucile Canterel-Thouennon, Arthur Hsu, Kym Pham, Ebba Louise Lagerqvist, Michel Prudhomme, Claire Philippe, Nathalie Rolland, Frédéric Hollande, Graham R. Taylor, Jean Christophe Boyer, Emmanuelle Charafe-Jauffret, Christina Mølck, Luke Zappia, Fanny Grillet, Jean-Marc Pascussi, Julie Pannequin, Olivia Villeronce, Sebastian Lunke |
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Přispěvatelé: | Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), University of Melbourne, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Laboratoire de Biochimie [CHRU Nîmes], Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Biochimie et Physiologie Moléculaire des Plantes (BPMP), Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Herrada, Anthony, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Colorectal cancer Cellular differentiation Biology Metastasis LIVER METASTASES 03 medical and health sciences 0302 clinical medicine Cancer stem cell medicine Cytotoxic T cell neoplasms COLORECTAL CANCER DRUG TOXICITY Gastroenterology Cancer [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology medicine.disease [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology digestive system diseases 3. Good health 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer research Ex vivo |
Zdroj: | Gut Gut, BMJ Publishing Group, 2017, 66 (10), pp.1802-1810. ⟨10.1136/gutjnl-2016-311447⟩ Gut, 2017, 66 (10), pp.1802-1810. ⟨10.1136/gutjnl-2016-311447⟩ |
ISSN: | 0017-5749 1468-3288 |
DOI: | 10.1136/gutjnl-2016-311447⟩ |
Popis: | International audience; OBJECTIVE:Although counting of circulating tumour cells (CTC) has attracted a broad interest as potential markers of tumour progression and treatment response, the lack of functional characterisation of these cells had become a bottleneck in taking these observations to the clinic. Our objective was to culture these cells in order to understand them and exploit their therapeutic potential to the full.DESIGN:Here, hypothesising that some CTC potentially have cancer stem cell (CSC) phenotype, we generated several CTC lines from the blood of patients with advanced metastatic colorectal cancer (CRC) based on their self-renewal abilities. Multiple standard tests were then employed to characterise these cells.RESULTS:Our CTC lines self-renew, express CSC markers and have multilineage differentiation ability, both in vitro and in vivo. Patient-derived CTC lines are tumorigenic in subcutaneous xenografts and are also able to colonise the liver after intrasplenic injection. RNA sequencing analyses strikingly demonstrate that drug metabolising pathways represent the most upregulated feature among CTC lines in comparison with primary CRC cells grown under similar conditions. This result is corroborated by the high resistance of the CTC lines to conventional cytotoxic compounds.CONCLUSIONS:Taken together, our results directly demonstrate the existence of patient-derived colorectal CTCs that bear all the functional attributes of CSCs. The CTC culture model described here is simple and takes |
Databáze: | OpenAIRE |
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