Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242514
Title: Novel roles for matrix metalloproteinases in cell-matrix interactions
Author: Messent, Anthea Jane
ISNI:       0000 0001 3395 452X
Awarding Body: Open University
Current Institution: Open University
Date of Award: 1998
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Abstract:
The aim of this study was to elucidate the effect of type I collagen degradation by a physiological enzyme on cell-collagen interactions. Type I collagen is degraded in vivo by collagenases, which are members of the matrix metalloproteinase family of enzymes. The ability of HT1080 cells, which express the major cell-surface collagen receptor α2β1 integrin, to attach to and invade through collagenase-cleaved collagen was investigated in cell attachment and invasion assays in comparison with the intact molecule. Binding studies of purified, platelet α2β1 integrin, and of ligand-binding A domain of this integrin to native collagen and to purified 3/4 and 1/4 fragments of collagen, generated by collagenase-3 revealed the necessity for retention of the triple-helical conformation of the collagen fragments for α2β1 integrin binding. HT1080 cell attachment to type I collagen was α2β1 integrin-mediated, and collagenase-cleavage of type I collagen perturbed cell attachment via this integrin at physiological temperature. This is likely to be due to melting of the collagen fragments, destabilizing of the triple-helical conformation of type I collagen and the resultant loss of α2β1 integrin binding sites on the collagen molecules. However, cell attachment to the native collagen fragments was still possible at room temperature, indicating that collagenase does not destroy α2β1 integrin binding sites on type I collagen, and that attachment can occur below physiological temperature. HT1080 cell invasion assays through equivalent molar concentrations of native type I collagen and the 3/4 and 1/4 fragments of collagen revealed that HT 1080 cell invasion through both collagen fragments was significantly greater relative to cell invasion through native collagen. These results may reflect the decreased adhesion to heat-unwound collagen fragments seen in attachment assays. Collagenase degradation of type I collagen significantly alters α2β1 integrin-mediated cell interactions with collagen, and also results in increased cell invasion through the degraded substrate. Matrix metalloproteinases may thus have an important role in cell-collagen interactions during tumour invasion and metastasis, where upregulation of matrix metalloproteinase synthesis by tumour and stromal cells is often observed.
Supervisor: Not available Sponsor: Cancer Research Campaign UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.242514  DOI:
Keywords: Cell adhesion; Cell motility; Collagenase
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