Expression of cathepsin K in chordoma

Invasive growth of chordoma is accompanied by severe destruction of adjacen t bone tissue, a fact that requires high proteolytic activity at the tumor invasion fronts. In this context, cathepsin K is a candidate molecule. It i s a protease with high collagenolytic and elastinolytic activity and previo usly thought to be restricted to osteoclasts and osteoclast-mediated bone r esorption. In this study, 44 cases of chordoma of sphenooccipital localizat ion, and 10 embryo-fetal specimens including chorda dorsalis were studied i mmunohistochemically for their expression of cathepsin It In 4 additional s nap-frozen chordoma cases, the enzyme expression was investigated by revers e transcription polymerase chain reaction and enzyme histochemistry. Ten ch ondrosarcomas of the skull base served as controls. Various concentrations of cathepsin K mRNA could be seen in all snap-frozen chordoma specimens. Th e protease was immunohistochemically expressed by the tumor cells. The immu noreactions were accentuated at the tumor invasion fronts. Enzyme histochem istry indicated a strong tumor cell-associated cathepsin K activity in inva sive tumor components. In contrast to chordoma, cathepsin K was not signifi cantly expressed in chorda dorsalis and chondrosarcoma of the skull base. I n chondrosarcoma, protease expression was limited to osteoclastic cells loc alized between infiltrative tumor components and regular bone trabeculae. T his study shows the significant expression and activity of cathepsin K in c hordoma and implicates an important and direct role of this protease in the infiltrative growth of this tumor. This protease expression occurred durin g neoplastic transformation and did not appear in chorda dorsalis. Copyrigh t (C) 2000 by W.B. Saunders Company.