The study of tumor vessel growth inhibiton Angiostatin, new mechanism of action and clinical application

• Project/Area Number: 13670496
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: MITSUI Hiroshi The University of Tokyo, The University of Tokyo Faculty of Medicine, Research (30239280)
• Co-Investigator(Kenkyū-buntansha): MARUYAMA Toshiyuki The University of Tokyo, Faculty of Medicine, Lecturer (30219571) ; SAKATA Yoichi 自治医科大学, Jichi Medical School Heamatology, Associate Professor (40129028)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: Angiostain / liver endothelial cells / 腫瘍血管

Research Abstract

Angiostatin (AG) is a product of which a coagulation factor with klingle structure, such as Plasminogen(PL) is cleaved. AG was reported to have capacity to inhibit the growth of cancer cells in vivo. In this study, we examine the mechanism and clinical application of AG. Among the human liver cancer cell lines examined, only Huh-7 cells can cleave purified PL, and produce AG. Human macrophage metalloesterase, a candidate of the cleaving enzyme, is expressed in all cell lines. We next used primary liver endothelial cell culture and add purified AG. From human plasma, PL was purified and then cleaved by elastase, and purified again. Rat liver endothelial cells were purified by collagenase perfusion and percoll centrifugation. AG inhibited endothelial cells growth and the effect depended on bFGF pathway. In another study, 30% of the patients of hepatocellular carcinoma had AG in their plasma judging by Western blotting. We tried immunological staining of liver cancer cell lines and found that HepG2 cells may express ATP synthase, which had been reported as a surface receptor of AG. We will examine that AG could inhibit malignant phenotypical change, such as cadherin E to N type, using this cells.

Research Products

• [Journal Article] The MEK-ERK MAP Kinase pathuay and the P13-Kinase-Akt pathway independently mediate anti-apoptotic signals in HepG2 liver caneor celle (2001)
  • Author(s): Mitsui H., et al.
  • Journal Title: Int J Cancer 92 Pages: 55-62
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] IgG_1 anti-P_2 as a marker of response to interferon in patients with chronic hepatitis C (2001)
  • Author(s): Hirayama M, et al.
  • Journal Title: Clin Exp Immunol 126 Pages: 92-100
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Esophageal smooth murcle fumor in a 25-year-old woman with congenital malformations (2001)
  • Author(s): Maekawa H., et al.
  • Journal Title: J Gastroenterol 36 Pages: 700-703
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The MEK1-ERK map kinase pathway and the PI 3-kinase-Akt pathway independently mediate anti-apoptotic signals in HepG2 liver cancer cells. (2001)
  • Author(s): Mitsui H, Takuwa N, Maruyama T, Maekawa H, Hirayama M, Sawatari T, Hashimoto N, Takuwa Y, Kimura S.
  • Journal Title: Int J Cancer. 92(1) Pages: 55-62
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] IgGi anti-P2 as a marker of response to interferon in patients with chronic hepatitis C. (2001)
  • Author(s): Hirayama M, Maruyama T, Mitsui H, Maekawa H, Yamada H, Hashimoto N, Koike K, Kimura S, Yasuda K, Iino S, Green J.
  • Journal Title: Clin Exp Immunol. 126(1) Pages: 92-100
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Esophageal smooth muscle tumor in a 25-year-old woman with congenital malformations. (2001)
  • Author(s): Maekawa H, Tanaka N, Hashimoto N, Yamada H, Mitsui H, Ikeda H, Maruyama T, Mori M, Nagawa H, Kimura S.
  • Journal Title: J Gastroenterol. 36(10) Pages: 700-703
  • NAID: 50000970489
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Mitsui H. et al.: "The MEKI-ERK MAP kinase pathway and the PI3-Kinase-AKT pathway mdependently mediate anti-apoptotic signals in HepG_2 cells"Int.J.Cancer. 92・1. 55-62 (2001)
• [Publications] Hirayama M. et al.: "IgG1 anti-p2 as a marker of response to interferon in patients with chronic hepatitis C"Clin.Exp.Immunol.. 126. 92-100 (2001)
• [Publications] Mitsui H. et al.: "Severe acute interstitial pneumonia and gefitinib(correspondence)"Lancet. (in press).
• [Publications] Mitsui H, et al.: "The MEK1-ERK MAP Kinase pathway and the PI3-Kinase-Ake pathway independently mediate anti-apoptotic signals in HepG2 cells"Int J Cancer. 92・1. 55-62 (2001)
• [Publications] Hirayama M, et al.: "1gG, anti-P2 as a marker of response to interferon in Patients with chronic hepatitis C"Clin Exp Immunol. 126. 92-100 (2001)