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J. Biol. Chem., Vol. 276, Issue 21, 17949-17957, May 25, 2001
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From the Departments of Bone marrow is the primary site of metastasis in
patients with advanced stage prostate cancer. Prostate carcinoma cells
metastasizing to bone must initially adhere to endothelial cells in the
bone marrow sinusoids. In this report, we have modeled that interaction in vitro using two bone marrow endothelial cell (BMEC)
lines and four prostate adenocarcinoma cell lines to investigate the
adhesion mechanism. Highly metastatic PC3 and PC3M-LN4 cells were 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 prostate carcinoma cells. DU145 and LNCaP cells
were only weakly adherent and retained no cell surface HA. Maximal BMEC
adhesion and HA encapsulation were associated with high levels of HA
synthesis by the prostate carcinoma cells. 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 could contribute to preferential bone metastasis by
prostate carcinoma cells.
Hyaluronan Synthase Elevation in Metastatic Prostate Carcinoma
Cells Correlates with Hyaluronan Surface Retention, a Prerequisite for
Rapid Adhesion to Bone Marrow Endothelial Cells*
,,,,
, and**
Laboratory Medicine and
Pathology, ¶ Orthopaedic Surgery and Biochemistry,
University of Minnesota, Minneapolis, Minnesota 55455 and the
§ Rowe Program in Genetics, Department of Biological
Chemistry, University of California, Davis, California 95616
*
This work was supported by NCI, National Institutes of
Health Grant CA29995, National Research Service Award 1F32-CA84619-01 (to M. A. S.), and U.S. Army Medical Research Grant PC970519.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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