Studies on the proliferation and metastasis formation of human osteosarcomas

4年来，我们对人骨肉瘤的增殖和转移形成进行了实验和临床研究。主要研究结果如下：(1)建立了3个人骨肉瘤裸鼠移植瘤模型和1个人骨肉瘤细胞株。(2)含有可检测到的c-myc转录本的人骨肉瘤在裸鼠体内生长更快。人骨肉瘤c-fos m RNA水平升高，裸鼠自发性肺转移发生率高。(3)ras癌基因可激活小鼠成骨样细胞的病灶形成，而p53可抑制ras癌基因的作用。(4)建立了人成骨样细胞系。1Alpha25(OH)2D3诱导碱性磷酸酶和骨钙素的表达，而转化生长因子β1抑制这两种成骨特性的表达。(5)建立了两株针对人骨肉瘤高度特异性的抗人骨肉瘤相关抗原的单抗。这些单抗对骨恶性肿瘤的诊断具有潜在的应用价值。(6)分析多药耐药基因-1(MDR-1)与骨肉瘤预后的关系。含MDR-1的骨肉瘤患者预后明显不良。(7)制备了人骨形成蛋白和骨唾液酸蛋白II的单抗。这些MASB有望成为免疫组织化学诊断人类骨源性肿瘤的有用工具。(8)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。原发骨肉瘤通过β1整合素的α4亚基和可能的α5亚单位与纤维连接蛋白密切结合。

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.