Studies on the proliferation and metastasis formation of human osteosarcomas

人骨肉瘤增殖和转移形成的研究

• 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; 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

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.

在这四年中，我们已经对人骨肉瘤的增殖和转移形成进行了实验和临床研究。我们获得的结果如下：（1）我们在裸鼠上建立了三个可移植的人骨肉瘤，并在体外衍生自人骨肉瘤。 （2）含有可检测的c-myctranscrests的人骨肉瘤在裸鼠中生长更快。在人骨肉瘤中，C-FOS M RNA的水平升高，显示裸鼠自发性肺转移的速率高。 （3）鼠骨细胞系的焦点形成被RAS-联合基因激活，而p53抑制了它们。 （4）我们在体外建立了人类成骨细胞细胞系。 1alpha25（OH）_2D_3诱导碱性磷酸酶和骨钙素的表达，而TGFBETA_1降低了两种成骨细胞特性的表达。 （5）我们建立了两种针对人骨肉瘤相关抗原的单克隆抗体（mAb），这对人骨肉瘤高度特异。这些mAB可能可用于诊断骨恶性肿瘤。 （6）我们分析了人骨肉瘤的预后与多药耐药基因-1（MDR-1）的存在之间的关系。骨肉瘤CONTAN的MDR-1显然预后较差。 （7）针对从人骨骼纯净的两种蛋白质产生了针对人BGP和骨唾液酸蛋白II的mAb。这些MASB有望成为人类成骨肿瘤的免疫组织化学诊断的有用工具。 （8）我们研究了骨肉瘤组织中β_1整合素家族和细胞外基质配体的表达。主要的骨肉瘤通过alpha_4与纤连蛋白紧密相互作用，并可能是β_1整合素的alpha_5亚基。