| RRC ID |
6537
|
| Author |
Miyata S, Fukushima T, Kohama K, Tanaka H, Takeshima H, Kataoka H.
|
| Title |
Roles of Kunitz domains in the anti-invasive effect of hepatocyte growth factor activator inhibitor type 1 in human glioblastoma cells.
|
| Journal |
Hum Cell
|
| Abstract |
Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane-bound serine proteinase inhibitor having two extracellular Kunitz-type proteinase inhibitor domains (KD) namely KD-1 and KD-2. It efficiently inhibits hepatocyte growth factor activator, matriptase, hepsin, prostasin and trypsin. We have previously reported that the expression of HAI-1 suppresses the in vitro invasive capability of human glioblastoma cells. In this study we examined the role of each KD in the anti-invasive effect of HAI-1. Engineered over-expression of the mature membrane-form HAI-1 suppressed in vitro fibrin gel invasion of two human glioblastoma cell lines, U251 and YKG-1. The migratory activity on type IV collagen was also suppressed by the HAI-1 expression. These effects were not affected by the deletion of intracytoplasmic domain of HAI-1. A truncated secreted form of HAI-1 also suppressed in vitro invasion of the cells, indicating that the extracellular portion of HAI-1 was responsible for the anti-invasive effect. To determine the roles of each KD in the anti-invasive effect of HAI-1 in vitro, we constructed expression plasmids for HAI-1 with or without mutation at the P1 position of the reactive site of each KD. The results revealed that the proteinase inhibitor activity of N-terminal KD (KD-1) is responsible for the anti-invasion effect of HAI-1.
|
| Volume |
20(4)
|
| Pages |
100-6
|
| Published |
2007-11-1
|
| DOI |
10.1111/j.1749-0774.2007.00035.x
|
| PII |
HUC035
|
| PMID |
17949349
|
| MeSH |
Amino Acid Motifs
Glioblastoma / pathology*
Humans
Neoplasm Invasiveness
Protein Structure, Tertiary / physiology
Proteinase Inhibitory Proteins, Secretory / chemistry*
Proteinase Inhibitory Proteins, Secretory / genetics
Proteinase Inhibitory Proteins, Secretory / physiology*
Serine Proteinase Inhibitors / physiology*
Tumor Cells, Cultured
|
| IF |
3.463
|
| Times Cited |
19
|
|
WOS Category
|
CELL BIOLOGY
|
| Resource |
| Human and Animal Cells |
U251(RCB0461)
YKG1(RCB2110) |
