The oncogenic and druggable hPG80 (Progastrin) is overexpressed in multiple cancers and detected in the blood of patients
Autor: | Vahan Kepenekian, Veronique Saywell, Laurent Villeneuve, Benoit You, Pierre Liaud, Berengere Vire, Frederic Mercier, Delphine Maucort-Boulch, Winston Tan, Alexandre Prieur, Julien Soulé, Maud Flacelière, Philippe Elies, Manish Kohli, Olivier Glehen, Carole Langlois-Jacques, Fanny Belouin, Dominique Joubert, Thibault Mazard, E. Assenat, Marc Ychou, Lea Payen, Eric Morency, Marie Dupuy |
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Přispěvatelé: | Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Eurobiodev, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé (UBO UFR MSS), Université de Brest (UBO), Institut du Cancer de Montpellier (ICM), 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), Dpt of Oncology [Rochester], Mayo Clinic, Hospices Civils de Lyon (HCL), ECS Progastrin, Salvy-Córdoba, Nathalie, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2) |
Rok vydání: | 2020 |
Předmět: |
Male
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology 0301 basic medicine MESH: Protein Precursors Research paper MESH: Oncogenes Antibodies Neoplasm Colorectal cancer Druggability lcsh:Medicine MESH: Spheroids Cellular MESH: Gastrins Neutralization Cohort Studies MESH: Aged 80 and over 0302 clinical medicine Neoplasms Medicine MESH: Neoplasms MESH: Cohort Studies MESH: Organ Specificity Cancer Aged 80 and over MESH: Aged lcsh:R5-920 MESH: Middle Aged MESH: Kinetics Progastrin [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology MESH: Gene Expression Regulation Neoplastic General Medicine Middle Aged 3. Good health Peritoneal carcinomatosis Gene Expression Regulation Neoplastic Organ Specificity MESH: Young Adult 030220 oncology & carcinogenesis Immunohistochemistry Female lcsh:Medicine (General) Adult MESH: Cell Line Tumor Monitoring Blood biomarker Antineoplastic Agents [SDV.CAN]Life Sciences [q-bio]/Cancer General Biochemistry Genetics and Molecular Biology Young Adult 03 medical and health sciences [SDV.CAN] Life Sciences [q-bio]/Cancer Cancer stem cell Cell Line Tumor Spheroids Cellular MESH: Cell Proliferation Gastrins Humans RNA Messenger Protein Precursors Gene Aged Cell Proliferation MESH: RNA Messenger MESH: Humans hPG80 business.industry lcsh:R MESH: Adult Oncogenes medicine.disease MESH: Male Kinetics MESH: Antibodies Neoplasm 030104 developmental biology Cancer research MESH: Antineoplastic Agents Therapy business MESH: Female |
Zdroj: | EBioMedicine EBioMedicine, 2020, 51, pp.102574. ⟨10.1016/j.ebiom.2019.11.035⟩ EBioMedicine, Elsevier, 2020, 51, pp.102574. ⟨10.1016/j.ebiom.2019.11.035⟩ EBioMedicine, Vol 51, Iss, Pp-(2020) |
ISSN: | 2352-3964 |
Popis: | Background: In colorectal cancer, hPG80 (progastrin) is released from tumor cells, promotes cancer stem cells (CSC) self-renewal and is detected in the blood of patients. Because the gene GAST that encodes hPG80 is a target gene of oncogenic pathways that are activated in many tumor types, we hypothesized that hPG80 could be expressed by tumors from various origins other than colorectal cancers, be a drug target and be detectable in the blood of these patients. Methods: hPG80 expression was monitored by fluorescent immunohistochemistry and mRNA expression in tumors from various origins. Cancer cell lines were used in sphere forming assay to analyze CSC self-renewal. Blood samples were obtained from 1546 patients with 11 different cancer origins and from two retrospective kinetic studies in patients with peritoneal carcinomatosis or hepatocellular carcinomas. These patients were regularly sampled during treatments and assayed for hPG80. Findings: We showed that hPG80 was present in the 11 tumor types tested. In cell lines originating from these tumor types, hPG80 neutralization decreased significantly CSC self-renewal by 28 to 54%. hPG80 was detected in the blood of patients at significantly higher concentration than in healthy blood donors (median hPG80: 4.88 pM versus 1.05 pM; p |
Databáze: | OpenAIRE |
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