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LAMININ‐5 PROMOTES HUMAN LUNG CARCINOMA CELL INTRAVASATION
Author(s) -
VivinusNebot Mylene,
Rousselle Patricia,
Hautem Francis,
Marinkovich Peter M,
Bernard Alain
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.582
Subject(s) - intravasation , laminin , microbiology and biotechnology , biology , basement membrane , endothelial stem cell , endothelium , stromal cell , cell migration , cancer research , cell , pathology , in vitro , extracellular matrix , cancer cell , cancer , endocrinology , medicine , biochemistry , genetics
During intravasation, carcinoma cells first invade the vascular basement membrane (VBM) and next cross the endothelium in a basal toward apical orientation. Laminin‐10 (Ln‐10) is a major component of all adult VBMs whereas laminin‐5 (Ln‐5) expression is strikingly restricted to the VBM of lymphatic organs and the lung. Ln‐5 mediates cell adhesion, migration and invasion but its role in VBMs is unknown. Thus, we addressed the question of its possible role in lung carcinoma cell egress. We designed an in vitro model of intravasation in Boyden chambers and compared the reverse transendothelial migration (RTEM) of lung carcinoma cell lines through a confluent endothelial monolayer grown on Ln‐5+Ln‐10 or on Ln‐10 alone, in a basal toward apical orientation. We found that Ln‐5 strongly promoted RTEM and this effect was metalloproteinase dependent. MMP‐9 secretion was augmented in endothelial cells cultured on Ln‐5+Ln‐10 as well as Src activity. Moreover, expression of the tight junction associated molecule ZO‐1 was strongly diminished in endothelial cells cultured on Ln‐10+Ln‐5. These data highlight the effect of Ln‐5 on endothelial cells and suggest that Ln‐5 might facilitate transendothelial migration of lung carcinoma cells by loosening endothelial junctions through a mechanism involving Src, MMP‐9 and ZO‐1.