title: Effects of collagenase-cleavage of type I collagen on alpha2beta1 integrin-mediated cell adhesion.
abstract: In this paper we show that collagenase-3 cleavage of type I collagen has a marked effect on alpha2beta1 integrin-mediated interactions with the collagen fragments generated. Isolated alpha2beta1 integrin and alpha2 integrin A-domain were found to bind to both native collagen and native 3/4 fragment and, to a lesser degree, native 1/4 fragment. Whole integrin and integrin A-domain binding were lost after heat denaturation of the collagen fragments. At physiological temperature, cell adhesion to triple-helical 3/4 fragment via alpha2beta1 integrin was still possible; however, no alpha2beta1 integrin-mediated adhesion to the 1/4 fragment was observed. Unwinding of the collagen fragment triple helices by heating to physiological temperatures prior to adsorption to plastic tissue culture plates resulted in total abrogation of HT1080 cell attachment to either fragment. These results provide significant evidence in support of a role for matrix-metalloproteinase cleavage of the extracellular matrix in modifying cell-matrix interactions.
authors.affiliation: Strangeways Research Laboratory, Worts Causeway, Cambridge, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Messent
authors.forename: D S
authors.initials: DS
authors.lastname: Tuckwell
authors.forename: V
authors.initials: V
authors.lastname: Knäuper
authors.forename: M J
authors.initials: MJ
authors.lastname: Humphries
authors.forename: G
authors.initials: G
authors.lastname: Murphy
authors.forename: J
authors.initials: J
authors.lastname: Gavrilovic
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism* / Q000494:pharmacology*; D005354:Fibrosarcoma; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13; D008545:Melanoma; D051379:Mice; D009361:Neoplasm Invasiveness; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D038981:Receptors, Collagen; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000201:enzymology
chemical_list: D002352:Carrier Proteins; D016023:Integrins; D010446:Peptide Fragments; D038981:Receptors, Collagen; D003094:Collagen; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; C507083:Mmp13 protein, rat