Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis
- Creators
- Tichet, Mélanie
- Prod 'Homme, Virginie
- Fenouille, Nina
- Ambrosetti, Damien
- Mallavialle, Aude
- Cerezo, Michael
- Ohanna, Mickaël
- Audebert, Stéphane
- Rocchi, Stéphane
- Giacchero, Damien
- Boukari, Fériel
- Allegra, Maryline
- Chambard, Jean-Claude
- Lacour, Jean-Philippe
- Michiels, Jean-François
- Borg, Jean-Paul
- Deckert, Marcel
- Tartare-Deckert, Sophie
- Others:
- Centre méditerranéen de médecine moléculaire (C3M) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)
- chu de nice, Hôpital Pasteur, Laboratoire Central d'Anatomo Pathologie ; Hôpital Pasteur [Nice] (CHU)
- 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)
- CHU de Nice, Hôpital Archet 2, Service de Dermatologie ; Hôpital Archet 2 [Nice] (CHU)
- Institut de Biologie Valrose (IBV) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- INSERM, Fondation ARC et Fondation de France
- ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011)
Description
Disruption of the endothelial barrier by tumour-derived secreted factors is a critical step in cancer cell extravasation and metastasis. Here, by comparative proteomic analysis of melanoma secretomes, we identify the matricellular protein SPARC as a novel tumour-derived vascular permeability factor. SPARC deficiency abrogates tumour-initiated permeability of lung capillaries and prevents extravasation, whereas SPARC overexpression enhances vascular leakiness, extravasation and lung metastasis. SPARC-induced paracellular permeability is dependent on the endothelial VCAM1 receptor and p38 MAPK signalling. Blocking VCAM1 impedes melanoma-induced endothelial permeability and extravasation. The clinical relevance of our findings is highlighted by high levels of SPARC detected in tumour from human pulmonary melanoma lesions. Our study establishes tumour-produced SPARC and VCAM1 as regulators of cancer extravasation, revealing a novel targetable interaction for prevention of metastasis.
Abstract
International audience
Additional details
- URL
- https://hal.science/hal-01295443
- URN
- urn:oai:HAL:hal-01295443v1
- Origin repository
- UNICA