Tumor cell-substrate stabilization mediated by integrins

John T. Patton, Larry V. McIntire, David G. Menter, Garth L. Nicolson

Research output: Chapter in Book/Report/Conference proceedingConference contribution

5 Scopus citations

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 (αvβ35) 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 α5β1 overexpression. The levels 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. 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.

Original languageEnglish (US)
Title of host publicationMaterials Research Society Symposium Proceedings
PublisherPubl by Materials Research Society
Pages147-152
Number of pages6
ISBN (Print)1558992308
StatePublished - 1994
EventProceedings of the Biomaterials for Drug and Cell Delivery - Boston, MA, USA
Duration: Nov 29 1993Dec 1 1993

Publication series

NameMaterials Research Society Symposium Proceedings
Volume331
ISSN (Print)0272-9172

Other

OtherProceedings of the Biomaterials for Drug and Cell Delivery
CityBoston, MA, USA
Period11/29/9312/1/93

ASJC Scopus subject areas

  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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