Related Experiment Video
Updated: Mar 8, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Cathepsin K expression in castration-resistant prostate carcinoma: a therapeutical target for patients at risk for
Enrico Munari1,2, Luca Cima1, Francesco Massari3
1Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona - Italy.
Background:
The lysosomal cysteine protease cathepsin K is involved in bone remodeling and is also expressed in the peritumoral stroma of carcinomas arising from different organs. A new generation of cathepsin K inhibitors blocking the RANKL/RANK pathway are being developed. We sought to investigate cathepsin K expression in a cohort of castration-resistant prostate carcinomas.
Methods:
Sixteen cases of castration-resistant disease with at least 5 years of follow-up were selected from a cohort of 280 patients who underwent surgery. Cathepsin K was evaluated on formalin-fixed and paraffin-embedded tissue microarrays with 5 tissue spots per case. These were scored as high 2+ (≥30% of cells), low 1+ (<30% of cells) or zero (absence), distinguishing tumor cells and peritumoral stroma cells. Low (1+) and absence (0) of scoring were interpreted as negative, and high (2+) as positive.
Results:
The castration-resistant group was composed of 15 acinar adenocarcinomas and 1 neuroendocrine carcinoma, and all showed at least Gleason score 8 at prostatectomy. Two out of 16 cases (12%) scored positive for cathepsin K in tumor cells; and 5 of 16 cases (31%) scored positive in peritumoral stroma cells. The neuroendocrine and acinar subtypes of carcinoma with positive immunoexpression in neoplastic cells developed bone metastases after 4 and 5 years, respectively, and subsequently died.
Conclusions:
Patients affected by castration-resistant prostate carcinoma may be tested for cathepsin K, and a positive strong expression (2+) could be a useful predictive biomarker of response to targeted agents, aiding in the selection of patients eligible for these treatments.
Insights
Cathepsin K is present in castration-resistant prostate cancer. Strong expression may predict response to targeted therapies, aiding patient selection for treatment.
Area of Science:
- Oncology
- Biochemistry
- Pathology
Background:
- Cathepsin K, a lysosomal cysteine protease, is implicated in bone remodeling and found in carcinoma stroma.
- Emerging cathepsin K inhibitors target the RANKL/RANK pathway.
- Investigated cathepsin K expression in castration-resistant prostate carcinomas.
Purpose of the Study:
- To assess cathepsin K expression in tumor cells and peritumoral stroma of castration-resistant prostate cancer.
- To explore cathepsin K as a potential biomarker for targeted therapy selection.
Main Methods:
- Analyzed 16 castration-resistant prostate carcinoma cases using tissue microarrays.
- Scored cathepsin K expression (0, 1+, 2+) in tumor and stromal cells.
- Defined high expression (2+) as positive and low/absent (0, 1+) as negative.
Main Results:
- Cathepsin K was expressed in tumor cells in 12% (2/16) and in peritumoral stroma in 31% (5/16) of cases.
- Neuroendocrine and acinar subtypes with positive tumor cell expression developed bone metastases and died within 4-5 years.
- Gleason score 8 or higher was observed in all cases.
Conclusions:
- Positive, strong cathepsin K expression (2+) in castration-resistant prostate cancer may serve as a predictive biomarker.
- Testing for cathepsin K could help identify patients eligible for targeted therapies.
- This finding supports the use of cathepsin K as a predictive marker for treatment selection.
