Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis

• DOI: 10.1038/ncomms7993
• Publication Date: 2015-04-30T11:31:23Z
• Authors: Mélanie Tichet; Virginie Prod’Homme; Nina Fenouille; Damien Ambrosetti; Aude Mallavialle; Michael Cerezo; Mickaël Ohanna; Stéphane Audebert; Stéphane Rocchi; Damien Giacchero; Fériel Boukari; Maryline Allegra; Jean-Claude Chambard; Jean-Philippe Lacour; Jean-François Mic...; Jean-Paul Borg; Marcel Deckert; Sophie Tartare-De...
• Keywords: Extravasation; Leukocyte extravasation; Vascular permeability; Matricellular protein

Disruption of the endothelial barrier by tumour-derived secreted factors is a critical step in cancer cell extravasation and metastasis. Here, comparative proteomic analysis melanoma secretomes, we identify matricellular protein SPARC as novel vascular permeability factor. deficiency abrogates tumour-initiated lung capillaries prevents extravasation, whereas overexpression enhances leakiness, SPARC-induced paracellular dependent on VCAM1 receptor p38 MAPK signalling. Blocking impedes melanoma-induced extravasation. The clinical relevance our findings highlighted high levels detected tumour from human pulmonary lesions. Our study establishes tumour-produced regulators revealing targetable interaction for prevention Metastatic cells are thought to influence through but mechanisms unclear. authors melanoma-secreted major regulator that modulates intercellular junctions.