Effects of normal and neoplastic canine prostate tissue on bone formation and investigations on the origin of canine prostate carcinoma

Prostate cancer is a common cause of cancer in older men. Prostate cancer commonly metastasizes to bone and induces new woven bone formation (osteoblastic metastases), likely caused by paracrine effects of factors produced by prostate cancer cells and released from the bone matrix. There are few models of prostate cancer osteoblastic metastases. Canine prostate cancer is a good model for human disease. To develop a new model of osteoblastic metastases, we investigated the effect of hyperplastic canine prostate tissue on bone formation in the calvarium (skull cap) of nude mice. Canine prostate induced new bone formation with minor bone lysis and no fractures. Osteoclasts were increased. To identify factors involved in the new bone formation, we treated organ cultures of rat calvaria with canine prostate homogenate. Prostate homogenate stimulated calvarial alkaline phosphatase activity 4 to 6-fold greater than controls. Alkaline phosphatase stimulation was prevented by pretreatment with endothelin receptor antagonists, but not anti-parathyroid hormone-related protein or indomethacin. The effect of neoplastic prostate tissue on bone was investigated using a canine prostate carcinoma xenograft. The xenografts caused bone formation, bone lysis, and lung metastasis in nude mice. The tumor cells expressed PTHrP, cathepsin K, and keratin 7. We also investigated keratin 7 and arginine esterase as candidate markers to distinguish canine prostate carcinoma from bladder carcinoma. Keratin 7 expression was very similar in neoplastic prostate and bladder tissues. Arginine esterase enzyme activity was present in high levels in normal and some neoplastic prostate tissue, but low in normal and neoplastic bladder tissue. Arginine esterase may be a useful marker to distinguish these carcinomas.