Cathepsin K Expression and Activity in Canine Osteosarcoma

• Published in: Journal of veterinary internal medicine 2012-01, Vol.26 (1), p.126-134
• Main Authors: Schmit, J.M., Pondenis, H.C., Barger, A.M., Borst, L.B., Garrett, L.D., Wypij, J.M., Neumann, Z.L., Fan, T.M.
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Western - veterinary; Bone Density Conservation Agents - pharmacology; Bone Neoplasms - enzymology; Bone Neoplasms - veterinary; Bone resorption; Cathepsin K - biosynthesis; Cathepsin K - genetics; Cell Line, Tumor; Collagen Type I - metabolism; Cysteine protease; Dog Diseases - enzymology; Dogs; Immunohistochemistry - veterinary; Malignant osteolysis; Osteosarcoma - enzymology; Osteosarcoma - veterinary; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction - veterinary; RNA - chemistry; RNA - genetics; Surrogate marker; Transforming Growth Factor beta1 - pharmacology
• ISSN: 0891-6640; 1939-1676
• DOI: 10.1111/j.1939-1676.2011.00834.x

Background 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. Hypothesis 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. Animals Fifty‐one dogs with appendicular OS and 18 age‐ and weight‐matched healthy control dogs. Methods 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. Results 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.