Expression of heparanase in human tumor cell lines and human head and neck tumors.
Heparanase is an endo-beta-D-glucuronidase that can cleave heparan sulfate and has been implicated in tumor angiogenesis and metastasis. Recent studies have demonstrated that overexpression of heparanase in human tumors facilitates their invasion activity, thereby enhancing the metastatic potential of the tumors. We found that heparanase mRNA and heparanase protein were constitutively elevated in some human tumor cell lines and human head and neck tumors. Heparanase mRNA expression was increased in response to treatment with an inhibitor of DNA methylation in cells that normally express low levels of heparanase mRNA. Inhibition of DNA methylation did not enhance heparanase mRNA expression in the presence of cycloheximide. These results suggest that overexpression of heparanase mRNA in cancer cells might not be due to demethylation of the promoter region of the heparanase gene itself, rather the other gene(s), such as transcriptional factors that, in turn, regulate heparanase expression.
Simizu
Siro
S
Antibiotics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Ishida
Keisuke
K
Wierzba
Michal K
MK
Sato
Taka Aki
TA
Osada
Hiroyuki
H
D015153:Blotting, Western; D003513:Cycloheximide / Q000494:pharmacology; D019175:DNA Methylation; D005966:Glucuronidase / Q000096:biosynthesis* / Q000737:chemistry*; D006367:HeLa Cells; D006258:Head and Neck Neoplasms / Q000201:enzymology*; D006801:Humans; D009361:Neoplasm Invasiveness; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D000099175:Heparanase
D003513:Cycloheximide; D005966:Glucuronidase; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D000099175:Heparanase