| Project/Area Number |
03404046
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
ISHII Seiichi Sapporo Medical University Professor, 医学部, 教授 (20001000)
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| Co-Investigator(Kenkyū-buntansha) |
KOIWAI Soichiro Sapporo Medical University Assistant Professor, 医学部, 講師 (90045336)
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| Project Period (FY) |
1991 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥28,700,000 (Direct Cost: ¥28,700,000)
Fiscal Year 1994: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1993: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1992: ¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 1991: ¥10,200,000 (Direct Cost: ¥10,200,000)
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| Keywords | Oncogene / Tumor suppressor gone / Multidrug resistance gene-1 / Tumor associated antigen / Bone gla protein / Bone sialoprotein II / Integrin / Osteosarcoma / 熱ショック蛋白質hsc73 / 熱ショック蛋白質hsp90 / インテグリンVLA-4 / インテグリン受容体VCAM-1 / 転移 / ヒト骨芽細胞株(SV-HFO) / ヒト骨中Ca結合蛋白 / オステオネクチン / integrin beta family / ラミニン受容体 / multi drug resistance gene / osteosarcoma / osteocalcin / oncogene / monoclonal antibody / integrin / metastasis |
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| Research Abstract |
We have carried out experimental and clinical studies on the proliferation and metastasis formation of human osteosarcomas in these 4 years. Results we obtained are as follows : (1) We established three transplantable human osteosarcomas on to nude mice, and one cell line derived from human osteosarcoma in vitro. (2) Human osteosarcomas containing detectable c-myctranscripts grew more rapidly in nude mice. The level of c-fos m RNA was increased in human osteosarcomas showing high rate of spontaneous lung metastasis in nude mice. (3) Focus formations of murine osteoblastoid cell line was activated by ras-oncogene, while p53 suppressed them. (4) We established a human osteoblastoid cell line in vitro. 1alpha25 (OH) _2D_3 induced the expression of alkaline phosphatase and osteocalcin, while TGFbeta_1 reduced the expression of both osteoblastic properties. (5) We established two monoclonal antibodies (MAbs) against human osteosarcoma associated antigen which were highly specific for human osteosarcomas. Those MAbs were potentially useful for diagnosis of bone malignancy. (6) We analyzed the relationship between the prognosis of human osteosarcomas and the existence of multidrug resistance gene-1 (MDR-1). Osteosarcoma contaning MDR-1 showed apparently poor prognosis. (7) MAbs specific for human BGP and Bone sialoprotein II were produced against both proteins purified from human bones. These MAsb are expected to be a useful tool for immunohistochemical diagnosis of human osteogenic tumors. (8) We studied the expression of the member of the beta_1 integrin family and extracellular matrix ligands in osteosarcoma tissues. Primary osteosarcomas closely interacted with fibronectin through alpha_4 and possibly alpha_5 subunits of the beta_1 integrin.
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