Skeletal metastasis of prostate adenocarcinoma in rats: Morphometric analysis and role of parathyroid hormone-related protein

BACKGROUND. Prostate cancer frequently metastasizes to bone, where it induc es osteoblastic lesions. Parathyroid hormone-related protein (PTHrP), a pro duct of normal and neoplastic prostate cells, may promote growth and bone m etastasis of certain types of cancer. In this study, we investigated the: 1 ) pathogenesis and morphology of bone metastases in the MATLyLu rat prostat e adenocarcinoma model, and 2) effect of PTHrP overexpression on tumor grow th and incidence of bone metastasis. METHODS. MATLyLu cells Mi ere stably transfected with a PTHrP expression ve ctor or control plasmid. PTHrP expression was determined in vitro by immuno radiometric assay and Northern blot analysis. MATLyLu cells were injected i nto the left ventricle of Copenhagen rats to induce bone metastases. Histol ogy and radiography were used to quantify the size and number of bone metas tases. Serum alkaline phosphatase isoenzyme concentrations and histomorphom etric analysis were used to evaluate bone formation and resorption. RESULTS. All rats developed osteolytic metastases-in long bones and vertebr ae. There was no evidence of increased intramedullary bone formation. PTHrP overexpression by MATLyLu cells was not associated with any difference in the incidence of bone metastasis, size of metastatic foci or tumor-cell pro liferation. CONCLUSIONS. The MATLyLu intracardiac injection model of prostate carcinoma is an aggressive tumor model with a high incidence of osteolytic skeletal metastases, and is not altered by increased PTHrP production by neoplastic prostate epithelial cells. (C) 1999 Wiley-Liss, Inc.