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The Osteoclast-associated Protease Cathepsin K Is Expressed in Human Breast Carcinoma¹

Novartis Pharma AG, CH-4002 Basel, Switzerland [A. J. L-E., G. B., D. F., D. B. E.]; Human Bone Cell Research Group, Department of Human Anatomy and Cell Biology [W. B. B., B. W., J. A. G.], and Department of Pathology [J. S.], University of Liverpool, Liverpool L69 3BX, United Kingdom [W. B. B., B. W., J. S., J. A. G.]; and Takarazuka Research Institute, Novartis Pharma Ltd., Takarazuka 665, Japan [T. K., T. I.]

Human cathepsin K is a novel cysteine protease previously reported to be restricted in its expression to osteoclasts. Immunolocalization of cathepsin K in breast tumor bone metastases revealed that the invading breast cancer cells expressed this protease, albeit at a lower intensity than in osteoclasts. In situ hybridization and immunolocalization studies were subsequently conducted to demonstrate cathepsin K mRNA and protein expression in samples of primary breast carcinoma. Expression of cathepsin K mRNA was confirmed by reverse transcription PCR and Southern analysis in a number of human breast cancer cell lines and in primary human breast tumors and their metastases. As this protease is known to degrade extracellular matrix, including bone matrix proteins, it is possible that cathepsin K may contribute to the invasive potential of breast cancer cells, including those that metastasize to bone. Thus, cathepsin K may be a potential target leading to the design of novel drugs for cancer therapy.

¹ To whom requests for reprints should be addressed, at Friedrich Miescher-Institute R1066.4.16, Maulbeer Strasse, Basel, CH4002, Switzerland. Phone: 061-6977876; Fax: 061-6973976; E-mail: littlam1@fmi.ch.

Received 7/10/97. Accepted 10/ 1/97.

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