Collagen degradation by tumor-associated trypsins

• Published in: Archives of biochemistry and biophysics Vol. 535; no. 2; pp. 111 - 114
• Main Authors: Mirigian, Lynn S., Makareeva, Elena, Koistinen, Hannu, Itkonen, Outi, Sorsa, Timo, Stenman, Ulf-Håkan, Salo, Tuula, Leikin, Sergey
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2013
• Subjects: collagen; Collagen degradation; Collagen Type I - chemistry; collagenase; Collagenolysis; denaturation; gel electrophoresis; Humans; Isoenzymes - chemistry; Matrix metalloproteinases; Neoplasms - chemistry; pancreas; Protein Denaturation; Protein Structure, Secondary; Protein Unfolding; tissues; Trypsin; Trypsin - chemistry; Tumor-associated trypsin; Collagenolysis; Trypsin; Collagen degradation; Matrix metalloproteinases; Tumor-associated trypsin
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2013.03.008

•We examined collagen degradation by non-sulfated trypsins commonly found in tumors.•Non-sulfated trypsins-1, -2, and -3 cleave only unfolded regions of collagen.•Trypsin-2 sulfation does not affect its collagenolytic activity.•Collagen cleavage by trypsin-2 reported earlier involved prior helix unfolding. 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.