Basic and clinical research on growth and metastasis of human osteosarcoma

用SEREX(重组表达克隆抗原血清学鉴定)方法鉴定人骨肉瘤相关抗原。共鉴定出8个候选基因。其中包括编码1型前胶原蛋白和c-myc结合蛋白同源基因。采用骨肉瘤细胞系(OS2000)及其细胞毒性T淋巴细胞克隆(CTL)。鉴定了由1，9O0碱基对基因编码的人类白细胞抗原A24和B55限制性分子，并用腺病毒载体将B7共刺激家族成员B7-1基因导入体内大鼠骨肉瘤细胞。观察对原发骨肉瘤的疗效免疫和对肺转移的系统免疫。B7-1a分子在B7家族成员中诱导最有效的共刺激信号，并比较了相同骨肉瘤原发灶和肺转移灶中ErbB2基因的表达。…的丢失随着原发灶的转移，14例患者ErbB2表达增强。在初诊时无转移的高级别骨肉瘤患者中，接受手术和化疗的患者中，肿瘤细胞中ErbB2水平的升高与无事件和总体生存的可能性显著增加相关。血管内皮生长因子(VEGF)在未经治疗的骨肉瘤中的表达预示着接受积极治疗的患者的肺转移和不良预后。此外，治疗前血清VEGF水平反映了原发肿瘤的血管生成特性，对骨肉瘤的早期疾病复发有预测价值。为了确定EWS-ETS融合蛋白的下游靶点，我们将EWS-ETS导入人纤维肉瘤细胞系。在表达EWS-ETS的细胞中，Tenascin-C的诱导水平显著高于表达正常EWS-Ets的细胞。由于Tenascin-C的表达与肿瘤的侵袭和恶性表型有关，EWS-ETS的致癌作用可能部分通过上调Tenascin-C的表达来实现。较少

Human osteosarcom associated antigens were identified by using SEREX (serological identification of antigen by recombinant expression cloning) method. Eight candidate genes were identified. They included the genes encoding procollagen type 1 and c-myc binding protein homologue.Human osteosarcoma associated antigen was identified with expression cloning method. The osteosarcoma cell line (OS2000) and its cytotoxic T-lymphocyte clone (CTL) were used. An HLA-A24 and B55 restricted molecule encoded by 1, 9O0-base pair gene was identified.B7-1 gene, a member of B7 costimulatory family, was introduced to rat osteosarcoma cells in vivo by using adenovirus vector. Curative immunity against primary osteosarcoma and systemic immunity against pulmonary metastasis was observed. B7-1a molecule induced the most efficacious costimulatory signal among B7 family members.Expression of ErbB2 gene was compared between the primary and pulmonary metastatic lesions of the same osteosarcoma patients. Loss of … More ErbB2 expression was noted in 14 of 19 patients as the primary tumor became metastatic. In patients with high-grade osteosarcoma without metastatic disease at presentation and treated with surgery and chemotherapy, the presence of increased level of ErbB2 in tumor cells is associated with a significantly increased probability of event-free and overall survival.Vascular endothelial growth factor (VEGF) expression in untreated ostesarcoma is predictive of pulmonary metastasis and poor prognosis in patients who underwent aggressive therapy. In addition, the pre-therapeutic serum VEGF level reflects tne angiogenic property of primary tumor and has a predictive value on early disease relapse of osteosarcoma.To identify downstream targets of EWS-ETS fusion protein, we introduced EWS-ETS into a human fibrosarcoma cell line. Tenascin-C is induced to a significantly higher level in cells expressing EWS-ETSs than in cells expressing normal EWS-ETS. As Tenascin-C expression is involved in the invasive and malignant phenotype, the oncogenic effect of EWS-ETS may be mediated in part by upregulating of Tenascin-C expression. Less