New bone formation and osteolysis by a metastatic, highly invasive canine prostate carcinoma xenograft.
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.
LeRoy
Bruce E
BE
Department of Pathology, University of Georgia, Athens, GA, USA.
Thudi
Nanda K
NK
Nadella
Murali V P
MV
Toribio
Ramiro E
RE
Tannehill-Gregg
Sarah H
SH
van Bokhoven
Adrie
A
Davis
Deborah
D
Corn
Stephanie
S
Rosol
Thomas J
TJ