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Search for molecules which bind to SCC antigen, analysis of their functions and clinical significance, and application to the molecular target therapy

寻找SCC抗原结合分子，分析其功能和临床意义，及其在分子靶向治疗中的应用

基本信息

批准号：
20591950
负责人：
MURAKAMI Akihiro
金额：
$ 3.16万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

The SCC antigen binds to the protein, which was identified to be carbonyl reductase (CR). The immunostaining analyses revealed that CR is located in the cytoplasm of keratinocytes and the normal squamous epithelial cells of the uterine cervix as well as SCCA1 and SCCA2. Sense and antisense CR cDNAs were transfected into a human uterine SCC cell lines to investigate the role of CR in cancer cell invasion and metastasis. In an in vitro experiment, suppression of CR showed morphology changes to like fibroblast, increased cancer cell invasion, secretion of MMP. On the other hand, over-expression of CR decreased MMP secretion. Paraffin sections from uterine cervical SCC tissues, FIGO stage Ib1-IIb were immunostained with anti-CR antibodies. Overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan-Meier method. Immunohistochemical analyses showed that reduced CR expression patterns in primary cancer lesions were closely associated with a high incidence of pelvic lymph node metastasis, poor OS, and poor PFS.

SCC抗原结合到蛋白质上，该蛋白质被鉴定为羰基还原酶（CR）。免疫组化结果显示，CR定位于角质形成细胞和正常宫颈鳞状上皮细胞以及SCCA 1和SCCA 2的细胞质中。将正义和反义CR cDNA转染人子宫鳞癌细胞系，研究CR在癌细胞侵袭和转移中的作用。在体外实验中，CR的抑制表现为形态学变化，类似成纤维细胞，癌细胞侵袭增加，MMP分泌增加。另一方面，CR的过度表达降低MMP的分泌。用抗CR抗体对FIGO Ib 1-IIb期宫颈SCC组织的石蜡切片进行免疫染色。采用Kaplan-Meier法分析总生存期（OS）和无进展生存期（PFS）。免疫组化分析显示，原发癌病灶中CR表达模式降低与盆腔淋巴结转移发生率高、OS差和PFS差密切相关。