Diverse roles of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in the growth of glioblastoma cells in vivo

Miyata, Shiro; Uchinokura, Shunro; Fukushima, Tsuyoshi; Hamasuna, Ryouichi; Itoh, Hiroshi; Akiyama, Yutaka; Nakano, Shinichi; Wakisaka, Shinichiro; Kataoka, Hiroaki

doi:10.1016/j.canlet.2005.01.010

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Volume 227, Issue 1 , Pages 83-93, 8 September 2005

Diverse roles of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in the growth of glioblastoma cells in vivo

Shiro Miyata
- Second Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
- Department of Neurosurgery, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
Shunro Uchinokura
- Second Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
- Department of Neurosurgery, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
Tsuyoshi Fukushima
- Second Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
- Department of Neurosurgery, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
Ryouichi Hamasuna
- Department of Neurosurgery, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
Hiroshi Itoh
- Second Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
Yutaka Akiyama
- Second Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
Shinichi Nakano
- Department of Neurosurgery, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
Shinichiro Wakisaka
- Department of Neurosurgery, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
Hiroaki Kataoka
- Second Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
- Corresponding author. Tel.: +81 985 85 2809; fax: +81 0985 85 6003.

Received 10 November 2004; received in revised form 14 December 2004; accepted 7 January 2005.

Abstract

Hepatocyte growth factor activator inhibitor type-1 (HAI-1) is an integral-membrane proteinase inhibitor. In this study, we examined the effects of HAI-1 on human glioblastoma cells. Two glioblastoma cell lines (YKG-1, U251) were stably transfected with expression plasmid harboring mature membrane-form or truncated secreted-form HAI-1. Culture characteristics were not altered by the expression of HAI-1, whereas in vitro invasiveness of U251 was suppressed. On the other hand, the expression of membrane-form HAI-1 resulted in significantly enhanced tumorigenicity of both cell lines in vivo. In contrast, secreted-form HAI-1 did not promote the tumorigenicity. These results suggest that HAI-1 may play complex roles in progression of glioblastoma cells, and membrane-form HAI-1 may mediate an undefined important signaling in the cells.

Keywords: Glioblastoma, HAI-1, Protease inhibitor, Hepatocyte growth factor (HGF), HGF activator