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

被引：149

作者：

Tichet, Melanie ^{[1
,2
]}

Prod'Homme, Virginie ^{[1
,2
]}

Fenouille, Nina ^{[1
,2
]}

Ambrosetti, Damien ^{[2
,3
]}

Mallavialle, Aude ^{[1
,2
]}

Cerezo, Michael ^{[2
,4
]}

Ohanna, Mickael ^{[2
,4
]}

Audebert, Stephane ^{[5
]}

Rocchi, Stephane ^{[2
,4
]}

Giacchero, Damien ^{[2
,6
]}

Boukari, Feriel ^{[1
,2
,6
]}

Allegra, Maryline ^{[2
,4
]}

Chambard, Jean-Claude ^{[2
,7
]}

Lacour, Jean-Philippe ^{[2
,6
]}

Michiels, Jean-Francois ^{[2
,3
]}

Borg, Jean-Paul

Deckert, Marcel ^{[1
,2
]}

Tartare-Deckert, Sophie ^{[1
,2
]}

机构：

[1] INSERM, C3M, Microenvironm Signalisat & Canc, U1065, F-06204 Nice, France

[2] Univ Nice Sophia Antipolis, Fac Med, F-06107 Nice, France

[3] CHU Nice, Hop Pasteur, Lab Cent Anatomo Pathol, F-06002 Nice, France

[4] INSERM, C3M, Biol & Pathol Melanocytes, U1065, F-06204 Nice, France

[5] Aix Marseille Univ, CNRS, CRCM, INSERM,Inst Paoli Calmettes,UMR7258,U1068, F-13273 Marseille, France

[6] CHU Nice, Hop Archet 2, Serv Dermatol, F-06202 Nice, France

[7] Fac Sci, iBV, CNRS, INSERM,UMR 7277,U1091, F-06108 Nice, France

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

HUMAN-MELANOMA CELLS; MESENCHYMAL TRANSITION; CANCER METASTASIS; PROGENITOR CELLS; PROTEIN SPARC; VE-CADHERIN; EXPRESSION; CYSTEINE; RICH; INVASION;

D O I：

10.1038/ncomms7993

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15

共 56 条

[1] A high-throughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis [J].