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Tumor Cell - Substrate Stabilization Mediated by Integrins

Published online by Cambridge University Press:  15 February 2011

John T. Patton ,
Larry V. McIntire ,
David G. Menter  and
Garth L. Nicolson
John T. Patton
Affiliation:
Cox Laboratory for Biomedical Engineering and Institute of Biosciences and Bioengineering, Rice University, Houston Texas 77251
Larry V. McIntire
Affiliation:
Cox Laboratory for Biomedical Engineering and Institute of Biosciences and Bioengineering, Rice University, Houston Texas 77251
David G. Menter
Affiliation:
Department of Tumor Biology, The University of Texas M. D. Anderson Cancer Center, Houston Texas 77030
Garth L. Nicolson
Affiliation:
Department of Tumor Biology, The University of Texas M. D. Anderson Cancer Center, Houston Texas 77030
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Abstract

Metastasis formation is dependent on the arrest and stabilization of adhesive interactions to prevent detachment from secondary sites. Primary receptor-ligand interactions are not sufficient to maintain prolonged adhesive contacts without secondary events that lead to stabilization. Tumor cell arrest and stabilization were studied under physiologically relevant shear conditions. We used a parallel-plate flow chamber with surfaces coated with human plasma fibronectin or vitronectin. Our previous work suggested that stabilization of cells to immobilized proteins is in part attributed to transglutaminase covalently cross-linking cytoskeletal-integrin-fibronectin multiprotein complexes via lysine-glutamine linkages. To study the role of integrins in mediating arrest and initiating stabilization we used a human melanoma line (70w) and polyclonal antibodies that inhibit the function of the fibronectin (α5β1) and vitronectin (αvβ3/β5) integrin receptors. To confirm the role of integrins in initiating stabilization we used CHO (Chinese hamster ovary) cells selected for low levels of α5β1 integrin expression and integrin transfected CHO cells selected for α5βl overexpression. The level of fibronectin receptor surface expression was inversely related to the adhesion stabilization lag time. These studies confirmed that integrins are essential for mediating arrest and initiating stabilization. They also confirm that secondary events are necessary for complete stabilization to occur. Finally, it is important to note that the arrest and stabilization methods we have developed are capable of detecting biologic effects at far greater sensitivity than static adhesion assays. Some examples of pharmacologic agents or biomaterials effects that can be detected using stabilization assays include: 1) very low drug doses, 2) very low levels of peptide, carbohydrate, and antibody inhibitors, 3) slight modification of endogenous protein expression by antisense oligonucleotides or transfected genetic expression constructs.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 331: Symposium T – Biomaterials for Drug and Cell Delivery , 1993 , 147
Copyright
Copyright © Materials Research Society 1994

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