Manipulation of hyaluronan synthase expression in prostate adenocarcinoma cells alters pericellular matrix retention and adhesion to bone marrow endothelial cells.
Prostate cancer metastasis to bone marrow involves initial adhesion of tumor cells to the bone marrow endothelium, followed by transmigration and proliferation within the marrow. Rapid, specific adhesion of highly metastatic prostate adenocarcinoma cells (PC3M-LN4) to bone marrow endothelial cell (BMEC) lines requires a pericellular hyaluronan (HA) matrix and correlates with dramatically up-regulated HA synthase (HAS) expression. Non-metastatic prostate tumor cells (LNCaP) do not assemble a HA matrix, adhere poorly to BMECs, and express normal levels of HAS. Preferential bone metastasis of prostate carcinoma cells may therefore be facilitated by tumor cell HA biosynthesis. In this report, HAS gene expression was manipulated to investigate the direct impact of prostate tumor cell HA production on adhesion to BMECs. PC3M-LN4 cells stably transfected with antisense HAS2 and HAS3 failed to form pericellular matrices. Adhesion of these transfectants to BMECs was significantly diminished, comparable to the low level exhibited by LNCaP cells. Upon transfection with full-length HAS2 or HAS3, the non-adherent LNCaP cells retained pericellular HA and adhered to BMECs. The results of this study are consistent with a model in which HA matrix formation, BMEC adhesion, and metastatic potential are mediated by HAS expression.
Simpson
Melanie A
MA
Department of Laboratory Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Wilson
Christopher M
CM
Furcht
Leo T
LT
Spicer
Andrew P
AP
Oegema
Theodore R
TR
McCarthy
James B
JB
D000230:Adenocarcinoma / Q000201:enzymology*; D001854:Bone Marrow Cells / Q000201:enzymology*; D002448:Cell Adhesion; D018076:DNA, Complementary / Q000378:metabolism; D004727:Endothelium / Q000166:cytology*; D005109:Extracellular Matrix / Q000378:metabolism*; D005434:Flow Cytometry; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000235:genetics; D016695:Glycosyltransferases; D006801:Humans; D000076002:Hyaluronan Synthases; D008297:Male; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology*; D011485:Protein Binding; D014162:Transfection; D014166:Transferases; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D029867:Xenopus Proteins
D018076:DNA, Complementary; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D029867:Xenopus Proteins; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases