Therapeutic induction of apoptosis into musculoskeletal tumors

Research Project

Project/Area Number	09671529
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Orthopaedic surgery
Research Institution	Kurume University
Principal Investigator	KOMIYA Setsuro Kurume Univ.School of Med.Associate Professor., 医学部, 講師 (30178371)
Co-Investigator(Kenkyū-buntansha)	ZENMYO Michihisa Kurume Univ.School of Med.Fellow, 医学部, 助手 (10289465) HIRAOKA Koji Kurume Univ.School of Med.Fellow, 医学部, 助手 (10268914)
Project Period (FY)	1997 – 1998
Project Status	Completed (Fiscal Year 1998)
Budget Amount *help	¥3,000,000 (Direct Cost: ¥3,000,000) Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000) Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywords	Osteosarcoma (OSA) / Giant cell tumor (GCT) / Fas / Soluble Fas / Apoptosis / Signal transduction
Research Abstract	Fas is a cell-surface antigen which could induce apoptosis, belonging to the superfamily of TNF-alpha. A study on Fas-mediated apoptosis has seldome been made in musculoskeletal tumors, including osteosarcoma. In this study using surgical samples and cell lines, Fas was searched in musculosketetal tumor cells, and the mechanism which could modulate Fas-mediated apoptosis was investigated. We also examined if apoptosis was induced in osteosarcoma cells by treatment with vitamins D and K.Furthermore, we investigated whether osteoclastoma cells could undergo apoptosis by treatment with bisphosphonates. In surgical samples, many positive cells were identified on TUNEL staining, and apoptotic bodies were seen in ultrastructural examinations. DNA samples demonstrated the ladder pattern characteristic to apoptosis. Fas was identified in 9 out of 14 osteosarcoma cell lines and in all of 4 osteoclastoma strains. The soluble form of Fas was also demonstrated. Treatment with cyclohexamide increased the induction of Fas-mdiated apoptosis in almost all of the cell lines. Treatment of osteosarcoma cells with vitamins D and K lead them to differentiation in accordance with the expression of p21, and apoptosis was then induced after the repression of p21. Bisphosphonates induced apoptosis in osteoclastoma cells. These results indicated that treat ment of those tumor cells to upregulate apoptosis may be essential for their treatment.