Purpose: To investigate the impact of prostate cancer cell surface glycosylation as part of the tumor cellendothelial cell interaction in prostate cancer metastasis.Experimental Design: Glycosyltransferase expression was profiled in metastasis-derived prostate cancer cell lines and compared with primary epithelium. Prostate cancer cells were examined for HPA-and selectinbinding and adhesion to endothelium. Spontaneous metastasis xenograft models were established to test the lectin HPA-binding sites as a marker of metastatic competence and to evaluate E-selectin-binding sites in vivo. The importance of selectins for metastasis formation was analyzed using Seleclinical relevance of HPA-and E-selectin-binding sites in prostate cancer was determined.Results: Glycosyltransferases involved in the synthesis of common HPA-binding sites are downregulated in prostate cancer cells. An absence of HPA-reactive carbohydrates specifically indicates spontaneous metastatic spread of prostate cancer xenografts in vivo and a poor prognosis of patients with prostate cancer. HPA-binding sites decrease in lymph node metastases compared with corresponding primary tumors. Common selectin ligands are absent on prostate cancer cells, which do not adhere to recombinant selectins or endothelium under shear stress in vitro. Spontaneous metastasis formation is largely independent of selectins in vivo. E-selectin-binding sites are detectable in only 2% of patients with prostate cancer without prognostic significance.Conclusion: Prostate cancer is characterized by an inverse functional and prognostic importance of HPAbinding sites compared with other adenocarcinomas. Accordingly, this study surprisingly shows that the selectin-selectin ligand axis, which is essential for extravasation and thus metastasis formation in several malignancies, can be circumvented in prostate cancer.

<p>PDF file 76K, Intrastromal PC-3 lung metastatic cells in E-/P-selectin-/- mice</p>

<p>PDF file 114K, supplementary M&M sections, Results and Figure Legends</p>