This study was conducted in the Veterinary Teaching Hospital at the University of Illinois, Urbana, IL.
Cathepsin K Expression and Activity in Canine Osteosarcoma
Article first published online: 15 DEC 2011
Copyright © 2011 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 26, Issue 1, pages 126–134, January-February 2012
How to Cite
Schmit, J.M., Pondenis, H.C., Barger, A.M., Borst, L.B., Garrett, L.D., Wypij, J.M., Neumann, Z.L. and Fan, T.M. (2012), Cathepsin K Expression and Activity in Canine Osteosarcoma. Journal of Veterinary Internal Medicine, 26: 126–134. doi: 10.1111/j.1939-1676.2011.00834.x
Partial results of this study were presented at the 29th Annual Veterinary Cancer Society Conference, Austin, TX.
- Issue published online: 10 JAN 2012
- Article first published online: 15 DEC 2011
- Manuscript Accepted: 5 OCT 2011
- Manuscript Revised: 26 SEP 2011
- Manuscript Received: 2 MAY 2011
- Bone resorption;
- Cysteine protease;
- Malignant osteolysis;
- Surrogate marker
Cathepsin K (CatK) is a lysosomal protease with collagenolytic activity, and its secretion by osteoclasts is responsible for degrading organic bone matrix. People with pathologic bone resorption have higher circulating CatK concentrations.
Canine osteosarcoma (OS) cells will possess CatK, and its secretion will be cytokine inducible. Circulating CatK concentrations will be increased in dogs with OS, and will be a surrogate marker of bone resorption.
Fifty-one dogs with appendicular OS and 18 age- and weight-matched healthy control dogs.
In a prospective study, expressions of CatK mRNA and protein were investigated in OS cells. The inducible secretion and proteolytic activity of CatK from OS cells was assessed in vitro. Serum CatK concentrations were quantified in normal dogs and dogs with OS and its utility as a bone resorption marker was evaluated in dogs with OS treated with palliative radiation and antiresorptive agents.
Canine OS cells contain preformed CatK within cytoplasmic vesicles. In OS cells, TGFβ1 induced the secretion of CatK, which degraded bone-derived type I collagen in vitro. CatK concentrations were higher in dogs with OS than healthy dogs (11.3 ± 5.2 pmol/L versus 8.1 ± 5.0 pmol/L, P = .03). In a subset of dogs with OS, pretreatment CatK concentrations gradually decreased after palliative radiation and antiresorptive treatment, from 9.3 ± 3.2 pmol/L to 5.0 ± 3.1 pmol/L, P = .03.
Conclusions and Clinical Importance
Canine OS is associated with pathologic bone resorption, and CatK inhibitors might aid in the management of canine OS-related malignant osteolysis.