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Signal transduction in melanoma transendothelial migration using a tissue‐engineered human blood vessel
Author(s) -
Auger François A.,
Fiola MarieChristine,
Tremblay PierreLuc,
Lacroix Dan,
Basoni Caroline
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.22.1_supplement.588.5
Subject(s) - rap1 , microbiology and biotechnology , signal transduction , cortactin , focal adhesion , biology , small gtpase , endothelial stem cell , actin cytoskeleton , cytoskeleton , cell , biochemistry , in vitro
Transendothelial migration involves major modifications in cell‐cell contact, consequent morphological changes and cytoskeletal reorganization. In this context, GTPases are key modulators in signal transduction leading to cellular modifications. Rap1, a member of the GTPase Ras Family, is implicated in the stability of endothelial adherent junctions. Rap1 is also implicated in integrin‐mediated adhesion of leukocytes to the endothelium, and participate in cadherin‐modulated adhesion. Those mechanisms are poorly understood, so further study is needed to elucidate the steps inherent to this process. We used a tissue‐engineered human blood vessel to analyze the role of Rap1 in the modulation of endothelial junctions. In endothelial cells monocultures, we observed that melanomas increased activated Rap1 and activated Extracellular Signal‐Regulated Kinase (Erk). We further analyzed the distribution of Zonula Occludens‐1 (ZO‐1) in endothelial tight junctions, and we observed a translocation to the nucleus when endothelial cells are stimulated with forskolin, a potent cAMP activator. We have to correlate those activations both with Rap1 signalling pathway and endothelial junctions remodelling. In the future, we will transpose those results using our 3D tissue‐engineered human blood vessels. Financial support is provided by the Canadian Institutes of Health Research.