Motile prostate cancer cell lines express vimentin. In tissue sections, the presence of vimentin positive tumour cells correlated positively to poorly differentiated cancers and the presence of bone metastases.

Objective To determine the E-cadherin and b-catenin expression phenotype in untreated primary prostate cancer and corresponding bone metastases. Materials and methods Paired bone metastasis and primary prostate specimens were obtained from 14 men with untreated metastatic prostate carcinoma. The tumours were histologically graded by an independent pathologist. Expression of mRNA for E-cadherin and b-catenin was detected within the tumour cells using in-situ hybridization with a 35 S-labelled cDNA probe. The expression of E-cadherin and b-catenin were graded as uniform, heterogeneous or negative. Results The mRNA for E-cadherin was expressed in 13 of 14 primary carcinomas and 11 bone metastases;b-catenin was expressed by 13 and nine, respectively. Of the primary tumours, nine expressed E-cadherin and b-catenin uniformly; in contrast, all metastases had down-regulated E-cadherin and/or b-catenin. Conclusions The down-regulation of E-cadherin and b-catenin are a feature of the metastatic phenotype, which may be a signi®cant factor in the genesis of bone metastases. However, this does not appear to be re¯ected in the expression of these molecules in the primary tumours.

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Prostate cancers ability to invade and grow in bone marrow stroma is thought to be due in part to degradative enzymes. The formation of prostate skeletal metastases have been reproduced in vitro by growing co-cultures of prostatic epithelial cells in bone marrow stroma. Expression of urokinase plasminogen activator, matrix metalloproteinase 1 and 7 by prostatic epithelial cells were identified using immunocytochemistry. Also, in vivo tissue sections from human prostatic bone marrow metastases were stained. To establish the role of these enzymes on colony formation, inhibitory antibodies directed against urokinase plasminogen activator, matrix metalloproteinase 1 and matrix metalloproteinase 7 were added into primary prostatic epithelial cells and bone marrow stroma co-cultures. All prostatic epithelial cell cultures stained positively for matrix metalloproteinase 1, matrix metalloproteinase 7 and urokinase plasminogen activator. Generally prostatic epithelial cells derived from malignant tissues showed increased staining in comparison to epithelia derived from non-malignant tissue. In agreement with in vitro co-cultures, the in vivo tissue sections of prostate bone marrow metastases showed positive staining for all three enzymes. Inhibition studies demonstrated that blocking matrix metalloproteinase 1, matrix metalloproteinase 7 and urokinase plasminogen activator function reduced the median epithelial colony area significantly in bone marrow stroma co-cultures in vitro. Using a human ex-vivo model we have shown that matrix metalloproteinase 1, matrix metalloproteinase 7 and urokinase plasminogen activator play an important role in the establishment of prostatic epithelial cells within bone marrow.