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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591950/
• 关键词: SCC抗原; carbonyl reductase (CR); 予後判定; carbonyl reductase; がんの浸潤・転移; 分子標的治療; 癌の浸潤・転移; 癌の予後診断

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抗原与蛋白质结合，该蛋白被确定为羰基还原酶（CR）。免疫染色分析表明，CR位于角质形成细胞的细胞质中，子宫颈的正常鳞状上皮细胞以及SCCA1和SCCA2。将感觉和反义CR CDNA转染到人子宫SCC细胞系中，以研究CR在癌细胞侵袭和转移中的作用。在体外实验中，CR的抑制显示出对成纤维细胞的形态变化，癌细胞侵袭增加，MMP的分泌。另一方面，CR的过表达降低了MMP分泌。从子宫宫颈SCC组织中的石蜡切片，FIGO IB1-IIB用抗CR抗体免疫染色。通过Kaplan-Meier方法分析了总生存期（OS）和无进展生存期（PFS）。免疫组织化学分析表明，原发性癌症病变中CR表达模式的降低与骨盆淋巴结转移的高发生率密切相关，OS差和PFS差。

项目成果

Carbonyl reductase, a binding molecule to SCC antigen

羰基还原酶，SCC 抗原的结合分子

• 发表时间: 2008
• 作者: Fukushima C;Murakami A
• 通讯作者: Murakami A

SCC抗原の結合分子carbonyl reductaseの機能解析と子宮頸部扁平上皮癌における臨床意義の解明

SCC抗原结合分子羰基还原酶的功能分析及其在宫颈鳞癌中的临床意义

• 发表时间: 2008
• 作者: Li L;Tanaka T;Yukawa K;Akira S;Umesaki N;苛原稔;Yoneyama K.;村上明弘
• 通讯作者: 村上明弘

SCC抗原の結合分子であるcarbonyl reductaseの機能解析とその臨床的意義の解明

SCC抗原结合分子羰基还原酶的功能分析及其临床意义的阐明

• 发表时间: 2008
• 作者: Tanaka T.;et al.;村上明弘
• 通讯作者: 村上明弘

子宮頸癌の検出方法

如何检测宫颈癌

• 发表时间: 2010

Identification and analysis of the intracellular molecules bound to SCC antigen.

与 SCC 抗原结合的细胞内分子的鉴定和分析。

• 发表时间: 2008
• 作者: Kajihara H;Yamada Y;Kanayama S;Furukawa N;Noguchi T;Haruta S;Yoshida S;Sado T;Oi H;Kobayashi H.;Nagai Y.;村上明弘
• 通讯作者: 村上明弘