Transglutaminase stabilizes melanoma adhesion under laminar flow |
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Authors: | D G Menter J T Patton T V Updyke R S Kerbel M Maamer L V Mcintire G L Nicolson |
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Institution: | 1. Department of Tumor Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 2. Laboratory for Biomedical Engineering, Institute for Biosciences and Bioengineering, Rice University, Houston, TX 3. Cancer Research Division, Sunnybrook Health Science Centre, M4N 3M5, Toronto, Ontario, Canada 4. Innothera Recherche, Arewell, Cedex, France
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Abstract: | To resist substantial wall shear stress (WSS) exerted by flowing blood, metastatic melanoma cells can form adhesive contacts
with subendothelial extracellular matrix proteins, such as fibronectin (FN). Such contacts may be stabilized by transglutaminase
catalyzed-crosslinkage of cell focal adhesion proteins. We analyzed human melanoma cell adhesion under flow by decreasing
the flow (WSS) of melanoma cell suspensions and allowing them to adhere to immobilized wheat germ agglutinin or FN. At the
wall shear adhesion threshold (WSAT), cell adherence was rapid with no rolling. Following cell adherence, we increased the
flow and determined the wall shear detachment threshold (WSDeT). Cells spread and remained adherent on immobilized FN at high
WSDeTs (≥ 32.5 dynes/cm2). The high resistance of adherent cells to shear forces suggested that transglutaminase-mediated crosslinking might be involved.
Transglutaminase inhibitors monodansylcadaverine and INO-3178 decreased WSAT, and at low concentrations completely inhibited
tumor cell spreading and promoted detachment at low WSDeTs (0.67 dynes/cm2). In static adhesion assays, transglutaminase inhibitors decreased cell adhesion to immobilized-FN in a dose-dependent manner
and prevented the formation of crosslinked125I-FN complex that failed to enter a SDS-polyacrylamide gradient gel. The data suggest that transglutaminase-catalyzed crosslinking,
particularly in the presence of WSS, may be important in stabilizing cellular adhesive contacts during adhesion to immobilized-FN. |
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Keywords: | Index Entries" target="_blank">Index Entries Parallel plate flow chamber wall shear stress transglutaminase tumor cell adhesion cell adhesion threshold cell detachment threshold cell spreading melanoma detergent-insoluble protein complex fibronectin integrin wheat germ agglutinin |
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