New Bone Formation and Osteolysis by a Metastatic, Highly Invasive Canine Prostate Carcinoma Xenograft

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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.

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