title: Collagen degradation by tumor-associated trypsins.
abstract: In normal soft tissues, collagen is degraded primarily by collagenases from the matrix metalloproteinase family. Yet, collagenase-like activity of tumor-associated isoforms of other enzymes might be involved in cancer invasion as well. In the present study, we systematically examined collagen degradation by non-sulfated isoforms of trypsins, which were proposed to possess such an activity. We found that non-sulfated trypsin-1, -2, and -3 were able to cleave non-helical and unfolded regions of collagen chains but not the intact triple helix, similar to sulfated trypsins produced by the pancreas. Trypsin-2 sulfation did not affect the cleavage rate either. An apparent triple helix cleavage by tumor-associated trypsin-2 reported earlier likely occurred after triple helix unfolding during sample denaturation for gel electrophoresis. Nevertheless, tumor-associated trypsins might be important for releasing collagen from fibers through telopeptide cleavage as well as for degrading unfolded collagen chains, e.g. after initial cleavage and destabilization of triple helices by collagenases.
authors.affiliation: National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lynn S
authors.initials: LS
authors.lastname: Mirigian
authors.forename: Elena
authors.initials: E
authors.lastname: Makareeva
authors.forename: Hannu
authors.initials: H
authors.lastname: Koistinen
authors.forename: Outi
authors.initials: O
authors.lastname: Itkonen
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
authors.forename: Ulf-Håkan
authors.initials: UH
authors.lastname: Stenman
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
authors.forename: Sergey
authors.initials: S
authors.lastname: Leikin
mesh_terms: D024042:Collagen Type I / Q000737:chemistry*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry; D009369:Neoplasms / Q000737:chemistry*; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D014357:Trypsin / Q000737:chemistry*
chemical_list: D024042:Collagen Type I; D007527:Isoenzymes; D014357:Trypsin
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