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Updated: May 12, 2026
05:48
Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion
Published on: March 18, 2014
Collagen degradation by tumor-associated trypsins
Lynn S Mirigian1, Elena Makareeva, Hannu Koistinen
1National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Archives of Biochemistry and Biophysics
|April 2, 2013
Summary
Non-sulfated trypsins (trypsin-1, -2, -3) can degrade unfolded collagen chains but not intact collagen triple helices. Tumor-associated trypsins may aid cancer invasion by processing collagen fibers.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Collagen degradation in soft tissues is mainly by matrix metalloproteinases.
- Tumor-associated enzymes may possess collagenase-like activity, contributing to cancer invasion.
- Trypsins have been proposed to exhibit collagen-degrading activity.
Purpose of the Study:
- To systematically investigate collagen degradation by non-sulfated trypsin isoforms.
- To determine if trypsin isoforms can cleave the intact collagen triple helix.
- To assess the role of trypsin sulfation in collagen cleavage activity.
Main Methods:
- Enzymatic assays using non-sulfated trypsin-1, -2, and -3.
- Analysis of collagen chain cleavage and triple helix integrity.
- Comparison with sulfated trypsin activity.
Main Results:
- Non-sulfated trypsin-1, -2, and -3 cleaved unfolded collagen chains but not intact triple helices.
- Collagen triple helix cleavage previously attributed to trypsin-2 likely resulted from sample denaturation.
- Trypsin-2 sulfation did not significantly alter collagen cleavage rates.
Conclusions:
- Non-sulfated trypsins exhibit limited collagenolytic activity, primarily on unfolded regions.
- Tumor-associated trypsins may contribute to cancer invasion by cleaving telopeptides and degrading unfolded collagen.
- The findings clarify the role of trypsins in collagen remodeling during cancer progression.
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