Cadherin-1 and cadherin-3 cooperation determines the aggressiveness of pancreatic ductal adenocarcinoma

Autor: Siret, Carole, Dobric, Aurélie, Martirosyan, Anna, Terciolo, Chloé, Germain, Sébastien, Bonier, Renaté, Dirami, Thassadite, Dusetti, Nelson, Tomasini, Richard, Rubis, Marion, Garcia, Stéphane, Iovanna, Juan, Lombardo, Dominique, Garcia, Stephane, Rigot, Veronique, André, Frédéric
Přispěvatelé: Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Marseille (CRCM), 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), service hospitalier d'anatomie et cytologie pathologique humaine, APHM, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM), Physiopathologie du stress pancréatique, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'anatomie pathologique - [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Nord [CHU - APHM]-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), 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), MITOYAN, Louciné
Rok vydání: 2017
Předmět:
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
endocrine system diseases
extracellular matrix
[SDV]Life Sciences [q-bio]
Cell
Pancreatic Intraepithelial Neoplasia
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
medicine.disease_cause
Collagen Type I
Metastasis
Mice
03 medical and health sciences
[SDV.CAN] Life Sciences [q-bio]/Cancer
Antigens
CD
Cell Movement
Cell Line
Tumor
Internal medicine
medicine
Animals
Humans
cancer
Molecular Diagnostics
Cell Proliferation
invadopodia
Cell growth
Cadherin
Cell Membrane
cell adhesion
Cell migration
Cadherins
invasion
medicine.disease
digestive system diseases
[SDV] Life Sciences [q-bio]
Pancreatic Neoplasms
030104 developmental biology
medicine.anatomical_structure
Invadopodia
Disease Progression
Cancer research
Carcinogenesis
Neoplasm Transplantation
Carcinoma
Pancreatic Ductal
Zdroj: British Journal of Cancer
British Journal of Cancer, Cancer Research UK, 2018, 118 (4), pp.546-557. ⟨10.1038/bjc.2017.411⟩
British Journal of Cancer, 2018, 118 (4), pp.546-557. ⟨10.1038/bjc.2017.411⟩
ISSN: 1532-1827
0007-0920
DOI: 10.1038/bjc.2017.411
Popis: International audience; Background: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an extensive tissue invasion and an early formation of metastasis. Alterations in the expression of cadherins have been reported in PDAC. Yet, how these changes contribute to tumour progression is poorly understood. Here, we investigated the relationship between cadherins expression and PDAC development.Cadherins expression was assessed by immunostaining in both human and murine tissue specimens. We have generated pancreatic cancer cell lines expressing both cadherin-1 and cadherin-3 or only one of these cadherins. Functional implications of such genetic alterations were analysed both in vitro and in vivo.RESULTS: Cadherin-3 is detected early at the plasma membrane during progression of pancreatic intraepithelial neoplasia 1 (PanIN-1) to PDAC. Despite tumoural cells turn on cadherin-3, a significant amount of cadherin-1 remains expressed at the cell surface during tumourigenesis. We found that cadherin-3 regulates tumour growth, while cadherin-1 drives type I collagen organisation in the tumour. In vitro assays showed that cadherins differentially participate to PDAC aggressiveness. Cadherin-3 regulates cell migration, whereas cadherin-1 takes part in the invadopodia activity.CONCLUSIONS: Our results show differential, but complementary, roles for cadherins during PDAC carcinogenesis and illustrate how their expression conditions the PDAC aggressiveness
Databáze: OpenAIRE
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