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
✍ Scribed by Ryouichi Hamasuna; Hiroaki Kataoka; Jing-Yan Meng; Hiroshi Itoh; Takuzou Moriyama; Shinichiro Wakisaka; Masashi Koono
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- French
- Weight
- 192 KB
- Volume
- 93
- Category
- Article
- ISSN
- 0020-7136
- DOI
- 10.1002/ijc.1349
No coin nor oath required. For personal study only.
✦ Synopsis
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 viv o and the effects of HAI-2/PB on the fibrinolytic and invasive capabilities of human glioblastoma cells in vitr o. 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 proteinasedependent matrix degradation. These findings suggest that the reduced expression of HAI-2/PB is possibly involved in the progression of human gliomas.