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
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