Journal
PROSTATE
Volume 66, Issue 11, Pages 1213-1222Publisher
WILEY
DOI: 10.1002/pros.20408
Keywords
prostate carcinoma; osteoblastic; osteolytic; canine; parathyroid hormone-related protein
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Funding
- NCI NIH HHS [CA 77911, T32 CA 09338] Funding Source: Medline
- NCRR NIH HHS [K26 RR 00168, RR 740027] Funding Source: Medline
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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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