Development of Gene Therapy for Lung Cancer using a Novel Antiangiogenic Factor BAI1

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11671325
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Okayama University
• Principal Investigator: FUJIWARA Toshiyoshi Okayama University, Hospital, Assistant, 医学部・附属病院, 助手 (00304303)
• Co-Investigator(Kenkyū-buntansha): KATAOKA Masafumi Okayama University, Hospital, Senior resident, 医学部・附属病院, 医員
• Project Period (FY): 1999 – 2000
• Keywords: Adenovirus / Heparanase / Antisense / Gene Therapy

Research Abstract

Heparan sulfate proteoglycans is a major component of the cell surface and extracellular matrix and functions as a barrier against cationic molecules and macromolecules. Heparanase is an endoglucuronidase capable of specifically degrading heparan sulfate and its activity is associated with metastatic potential of tumor cells. To inhibit human heparanase expression in human cancer cells, we constructed an adenoviral vector carrying a full-length human heparanase cDNA in an antisense orientation (Ad-AS/hep). Increased heparanase expression in T.Tn human esophageal cancer cells and A549 human lung cancer cells following infection with an adenovirus vector expressing human heparanase gene (Ad-S/hep) was specifically inhibited by simultaneous infection with Ad-AS/hep in a dose-dependent manner. A modified Boyden chamber assay demonstrated that infection with Ad-AS/hep significantly inhibited in vitro invasion of A549 cells following Ad-S/hep infection. Moreover, intrathoracic administration of Ad-AS/hep reduced the number and size of heparanase-expressing A549 tumors implanted intrathoracically into BALB/c nu/nu mice. Our results suggest that heparanase contributes to the invasive phenotype of tumor cells and that antisense-mediated inhibition of heparanase activity may be efficacious in the prevention of pleural dissemination.

Research Products

• [Publications] Uno Futoshi et al.: "Antisense-mediated suppression of human heparanase gene expression inhibits pleural dissemination of human cancer cells"Cancer Research. 61(21). 7855-7860 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Uno, R., Fujiwara, T., Takata, Y., Ohtani, S., Katsuda, K., Takaoka, M., Ohkawa, T., Naomoto, Y., Nakajima, M., Tanaka, N.: "Antisense-mediated suppression of human heparanase gene expression inhibits pleural dissemination of human cancer cells."Cancer Res.. 61 (21). 7855-60 (2001)
  • Description: 「研究成果報告書概要(欧文)」より