权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Studies on the proliferation and metastasis formation of human osteosarcomas

人骨肉瘤增殖和转移形成的研究

基本信息

批准号：
03404046
负责人：
ISHII Seiichi
金额：
$ 18.37万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03404046/
关键词：
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

项目摘要

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.

我们对人骨肉瘤的增殖和转移形成进行了4年的实验和临床研究。结果如下：（1）建立了三个人骨肉瘤裸鼠移植瘤模型和一个人骨肉瘤细胞系。(2)含有可检测到的c-myctranscripts的人骨肉瘤在裸鼠中生长得更快。人骨肉瘤中c-fos mRNA表达水平增高，裸鼠自发性肺转移率高。(3)ras癌基因激活小鼠成骨样细胞系的病灶形成，而p53抑制它们。(4)我们在体外建立了人成骨样细胞系。1 α 25（OH）_2D_3诱导碱性磷酸酶和骨钙素的表达，而TGF β_1降低这两种成骨特性的表达。(5)我们建立了两株抗人骨肉瘤相关抗原的单克隆抗体，它们对人骨肉瘤具有高度特异性。这些单克隆抗体对骨恶性肿瘤的诊断有潜在的应用价值。(6)分析多药耐药基因-1（MDR-1）的存在与骨肉瘤预后的关系。MDR-1阳性的骨肉瘤预后明显差。(7)针对从人骨中纯化的两种蛋白质产生对人BGP和骨唾液蛋白II特异的MAbs。这些MAsb有望成为人类成骨肿瘤免疫组化诊断的有用工具。(8)我们研究了β_1整合素家族成员和细胞外基质配体在骨肉瘤组织中的表达。原发性骨肉瘤通过β_1整合素的α_4和可能的α_5亚基与纤连蛋白密切相互作用。