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

Abstract

Prostate cancer frequently metastasizes to bone, where it induces osteoblastic lesions. Parathyroid hormone-related protein (PTHrP), a product of normal and neoplastic prostate cells, may promote growth and bone metastasis of certain types of cancer. In this study, we investigated the: 1) pathogenesis and morphology of bone metastases in the MATLyLu rat prostate adenocarcinoma model, and 2) effect of PTHrP overexpression on tumor growth and incidence of bone metastasis. MATLyLu cells were stably transfected with a PTHrP expression vector or control plasmid. PTHrP expression was determined in vitro by immunoradiometric assay and Northern blot analysis. MATLyLu cells were injected into the left ventricle of Copenhagen rats to induce bone metastases. Histology and radiography were used to quantify the size and number of bone metastases. Serum alkaline phosphatase isoenzyme concentrations and histomorphometric analysis were used to evaluate bone formation and resorption. All rats developed osteolytic metastases in long bones and vertebrae. 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 proliferation. 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.