Hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) are potential targets in uterine leiomyosarcoma

  • Authors:
    • Keiichiro Nakamura
    • Fernando Abarzua
    • Atsushi Hongo
    • Junichi Kodama
    • Yasutomo Nasu
    • Hiromi Kumon
    • Yuji Hiramatsu
  • View Affiliations

  • Published online on: September 1, 2010     https://doi.org/10.3892/ijo_00000709
  • Pages: 605-614
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Abstract

Hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) are Kunitz-type serine protease inhibitors that have a broad inhibitory spectrum against serine proteases. This study examined the role of HAI-1 and HAI-2 in uterine leiomyosarcoma (LMS) patients, and in vitro. HAI-1 and HAI-2 was examined in uterine normal smooth muscle, leiomyoma and LMS specimens using immunohistochemistry. We investigated biological functions and inhibitory effects of HAI-1 and HAI-2 using uterine LMS cell line SK-LMS-1 and SKN. The expression levels of HAI-1 and HAI-2 were significantly decreased in uterine LMS specimens relative to corresponding uterine normal smooth muscle and leiomyoma specimens. Furthermore, the low HAI-1 and HAI-2 expression was a significant predictor for poor prognosis when compared with high HAI-1 and HAI-2 expression (disease-free survival rate; p=0.024 and p=0.045, overall survival rate; p=0.043 and p=0.009). HAI-1 and HAI-2 showed potential inhibitory effects that mediated cell proliferation, migration and cellular invasion which led to apoptosis and necrosis through a reduction of HGFA, matriptase and hepsin expression. These findings indicate that HAI-1 and HAI-2 may be possible tumor suppressor genes for uterine LMS and thus, both could be considered therapeutic agents for the treatment of LMS.

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September 2010
Volume 37 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Nakamura K, Abarzua F, Hongo A, Kodama J, Nasu Y, Kumon H and Hiramatsu Y: Hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) are potential targets in uterine leiomyosarcoma. Int J Oncol 37: 605-614, 2010
APA
Nakamura, K., Abarzua, F., Hongo, A., Kodama, J., Nasu, Y., Kumon, H., & Hiramatsu, Y. (2010). Hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) are potential targets in uterine leiomyosarcoma. International Journal of Oncology, 37, 605-614. https://doi.org/10.3892/ijo_00000709
MLA
Nakamura, K., Abarzua, F., Hongo, A., Kodama, J., Nasu, Y., Kumon, H., Hiramatsu, Y."Hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) are potential targets in uterine leiomyosarcoma". International Journal of Oncology 37.3 (2010): 605-614.
Chicago
Nakamura, K., Abarzua, F., Hongo, A., Kodama, J., Nasu, Y., Kumon, H., Hiramatsu, Y."Hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) are potential targets in uterine leiomyosarcoma". International Journal of Oncology 37, no. 3 (2010): 605-614. https://doi.org/10.3892/ijo_00000709