RRC ID 72296
Author Hamasuna R, Kataoka H, Meng JY, Itoh H, Moriyama T, Wakisaka S, Koono M.
Title Reduced expression of hepatocyte growth factor activator inhibitor type-2/placental bikunin (HAI-2/PB) in human glioblastomas: implication for anti-invasive role of HAI-2/PB in glioblastoma cells.
Journal Int J Cancer
Abstract Hepatocyte growth factor activator inhibitor type-2/placental bikunin (HAI-2/PB) is a serine proteinase inhibitor that contains 2 Kunitz-domains and a presumed transmembrane domain. It has broad inhibitory spectra against various serine proteinases showing potent inhibitory activities not only to hepatocyte growth factor activator but also to plasmin, trypsin and kallikreins. In this study, we investigated the expression of HAI-2/PB in human gliomas in vivo and the effects of HAI-2/PB on the fibrinolytic and invasive capabilities of human glioblastoma cells in vitro. With RNA blot analysis, HAI-2/PB mRNA was expressed in normal brain and in low-grade astrocytomas, but was hardly detectable in anaplastic astrocytomas and glioblastomas, indicating that its expression levels were inversely correlated with the histological grade of human gliomas. To further explore the possible role of HAI-2/PB in glioma progression, cultured human glioblastoma cell lines (U251 and YKG-1) were transiently transfected with an expression vector harboring human HAI-2/PB cDNA. Subsequent analysis indicated that the expression of HAI-2/PB suppressed the fibrinolytic activities of both glioblastoma cell lines. Moreover, HAI-2/PB inhibited Matrigel invasion of U251 and YKG-1 cells by 30% and 64%, respectively. This anti-invasive effect appeared to be mediated primarily by the inhibitory activity of HAI-2/PB against the serine proteinase-dependent matrix degradation. These findings suggest that the reduced expression of HAI-2/PB is possibly involved in the progression of human gliomas.
Volume 93(3)
Pages 339-45
Published 2001-8-1
DOI 10.1002/ijc.1349
PII 10.1002/ijc.1349
PMID 11433397
MeSH Astrocytoma / genetics Astrocytoma / metabolism* Blotting, Northern Brain Neoplasms / genetics Brain Neoplasms / metabolism* Collagen / chemistry DNA Primers / chemistry Drug Combinations Fibrin / metabolism Glioblastoma / genetics Glioblastoma / metabolism* Hepatocyte Growth Factor / metabolism Humans Immunoblotting Laminin / chemistry Membrane Glycoproteins / genetics Membrane Glycoproteins / metabolism* Neoplasm Invasiveness Proteoglycans / chemistry Proto-Oncogene Proteins c-met / metabolism RNA / metabolism RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Serine Endopeptidases / metabolism Serine Proteinase Inhibitors / genetics Serine Proteinase Inhibitors / metabolism* Transfection Trypsin Inhibitor, Kunitz Soybean*
IF 5.145
Human and Animal Cells U251(RCB0461) KG-1-C(RCB0270)