Hyaluronan synthase elevation in metastatic prostate carcinoma cells correlates with hyaluronan surface retention, a prerequisite for rapid adhesion to bone marrow endothelial cells

Bone marrow is the primary site of metastasis in patients with advanced sta ge prostate cancer. Prostate carcinoma cells metastasizing to bone must ini tially adhere to endothelial cells in the bone marrow sinusoids. In this re port, we have modeled that interaction in vitro using two bone marrow endot helial cell (BMEC) lines and four prostate adenocarcinoma cell lines to inv estigate the adhesion mechanism. Highly metastatic PC3 and PC3M-LN4 cells w ere found to adhere rapidly and specifically (70-90%) to BMEC-1 and trHBMEC bone marrow endothelial cells, but not to human umbilical vein endothelial cells (15-25%). Specific adhesion to BMEC-1 and trHBMEC was dependent upon the presence of a hyaluronan (HA) pericellular matrix assembled on the pro state carcinoma cells. DU145 and LNCaP cells were only weakly adherent and retained no cell surface HA. Maximal BMEC adhesion and HA encapsulation wer e associated with high levels of HA synthesis by the prostate carcinoma cel ls. Up-regulation of HA synthase isoforms Has2 and Has3 relative to levels expressed by normal prostate corresponded to elevated HA synthesis and avid BMEC adhesion. These results support a model in which tumor cells with up- regulated HA synthase expression assemble a cell surface hyaluronan matrix that promotes adhesion to bone marrow endothelial cells. This interaction c ould contribute to preferential bone metastasis by prostate carcinoma cells .