Insulin receptor isoform A favors tumor progression in human hepatocellular carcinoma by increasing stem/progenitor cell features

Autor: Dominique Wendum, Olivier Scatton, Marie Lequoy, Christèle Desbois-Mouthon, Olivier Rosmorduc, Laura Fouassier, Fatiha Merabtene, Zeina Salamé, Yves Chrétien, Laetitia Fartoux, Eva Benabou, Françoise Praz, Sylvana Tahraoui
Přispěvatelé: Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Service d'hépatologie [Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Unité Mixte de Service d'Imagerie et de Cytométrie (UMS LUMIC), Service d'hépatologie [CHU Saint-Antoine], Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Gestionnaire, Hal Sorbonne Université, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine]
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Cancer Research
Carcinoma
Hepatocellular
Mice
Nude
[SDV.CAN]Life Sciences [q-bio]/Cancer
Mice
SCID
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
03 medical and health sciences
Mice
0302 clinical medicine
Downregulation and upregulation
[SDV.CAN] Life Sciences [q-bio]/Cancer
Invasion
Antigens
CD
Mice
Inbred NOD
Cell Line
Tumor
medicine
Animals
Humans
Protein Isoforms
Progenitor cell
Autocrine signalling
ComputingMilieux_MISCELLANEOUS
Liver Neoplasms
Cell migration
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Cytokeratin-19
medicine.disease
Immunohistochemistry
Receptor
Insulin
[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
digestive system diseases
3. Good health
Insulin receptor
030104 developmental biology
Oncology
Cell culture
Tumor progression
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Cancer research
biology.protein
Disease Progression
Neoplastic Stem Cells
Heterografts
Female
INSR
Liver cancer
Zdroj: Cancer Letters
Cancer Letters, Elsevier, 2019, 450, pp.155-168. ⟨10.1016/j.canlet.2019.02.037⟩
Cancer Letters, 2019, 450, pp.155-168. ⟨10.1016/j.canlet.2019.02.037⟩
ISSN: 0304-3835
Popis: International audience; Hepatocellular carcinoma (HCC) is one of the most common and deadly neoplasms. Insulin receptor (IR) exists in two isoforms, IR-A and IR-B, the latter being predominantly expressed in normal adult hepatocytes while IR-A is overexpressed in HCC to the detriment of IR-B. This study evaluated the biological functions associated with IR-A overexpression in HCC in relation to expression of its ligand IGF-II. The value of INSRA:INSRB ratio which was increased in ˜70% of 85 HCC was associated with stem/progenitor cell features such as cytokeratin-19 and α-fetoprotein and correlated with shorter patient survival. IGF2 mRNA upregulation was observed in 9.4% of HCC and was not associated with higher INSRA:INSRB ratios. Ectopic overexpression of IR-A in two HCC cell lines presenting a strong autocrine IGF-II secretion loop or not stimulated cell migration and invasion. In cells cultured as spheroids, IR-A overexpression promoted gene programs related to stemness, inflammation and cell movement. IR-A also increased cell line tumorigenicity in vivo after injection to immunosuppressed mice and the sphere-forming cells made a significant contribution to this effect. Altogether, these results demonstrate that IR-A is a novel player in HCC progression.
Databáze: OpenAIRE
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