New bone formation and osteolysis by a metastatic, highly invasive canine prostate carcinoma xenograft

Abstract
Background Osteoblastic metastases are commonly induced by prostate cancer. A canine prostate carcinoma xenograft (Ace‐1) was developed and used to evaluate neoplastic prostate cell growth, metastasis, and effects on bone formation in nude mice. Methods Characteristics of the Ace‐1 cells were evaluated with histopathology, radiography, and bioluminescent imaging (BLI). Immunohistochemistry and quantitative RT‐PCR were used to evaluate the expression of factors important in the development of osteoblastic metastases. Results The Ace‐1 cells were invasive and induced bone formation and destruction. Radiographs demonstrated a mixed osteoblastic/osteolytic reaction. Lung and lymph node metastases occurred in 30% of mice. The tumor cells expressed parathyroid hormone‐related protein (PTHrP‐141 isoform), cathepsin K, keratins 8/18, and vimentin, but not keratins 5/14, and were androgen receptor negative. Intracardiac (IC) injections resulted in metastases in vertebrae and long bones. Conclusions The Ace‐1 xenograft is a useful model for investigating the pathogenesis of prostate cancer invasion and mixed osteoblastic/osteolytic bone metastases. Prostate

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