Microenviroment and organ specific metastases in urological cancers as tools to elucidate molecular mechanism of carcinogenesis and tumor development.

泌尿系统癌症中的微环境和器官特异性转移作为阐明癌发生和肿瘤发展分子机制的工具。

• 批准号: 21390445
• 负责人: OYA Mototsugu
• 金额: $ 10.82万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390445/
• 关键词: 腎細胞癌; 分子標的治療; 上皮-間葉転換; Snail; 転移; 浸潤; E-cadherin; 骨転移; RANKL; RANK

Ninety-seven primary(renal cell carcinomas) RCCs were analyzed for the protein expression of Snail, Slug, MMP2 and MMP9 by immunohistochemistry. Snail protein expression level was positively correlated with pathological tumor stage, histological grade and the presence of sarcomatoid carcinoma. Because Snail was positively associated with malignant potential of RCCs, involvement of Snail in the invasiveness of an RCC cell lines 786-O and ACHN were examined in the Matrigel invasion assay by down-regulating the gene expression with small interfering RNA(siRNA). Invasion of the cells through Matrigel in vitro was inhibited under this condition. Furthermore, expression levels of MMP2 and MMP9 were positively correlated with pathological tumor stage and the presence of sarcomatoid carcinoma. In conclusion, these data suggest that Snail has an important role in invasion and metastasis, and that silencing the gene may be a potenal therapeutic target in RCCs.Receptor activator of NF-κB ligand(RANKL) and its receptor, receptor activator of NF-κB(RANK), play a key role in osteoclastogenesis RANKL protein expression level showed positive correlations with the primary tumour stage and distant metastasis. RANKL and RANK expression was observed in metastatic RCCs in the bone and other organs, suggesting that they play a role in metastasis to the bone and other organs. Recombinant RANKL protein stimulated migration of a clear cell RCC cell line, Caki-1, in vitro, and this enhanced migration was inhibited by the administration of recombinant OPG protein. These data suggest that the RANKL-RANK-OPG system is involved not only in the bone metastasis of RCCs but also in metastasis to other organs through the stimulation of cancer cell migration.

应用免疫组织化学方法检测97例肾细胞癌组织中Snail、Slug、MMP2和MMP9蛋白的表达。Snail蛋白表达水平与肿瘤病理分期、组织学分级及肉瘤样癌的存在呈正相关。由于Snail与肾癌的恶性潜能呈正相关，因此在Matrigel侵袭实验中，通过小干扰RNA(SiRNA)下调基因表达，研究了Snail与肾癌细胞株786-O和ACHN侵袭的关系。在此条件下，细胞通过Matrigel的体外侵袭被抑制。此外，MMP2和MMP9的表达水平与肿瘤的病理分期和肉瘤样癌的存在呈正相关。上述结果提示，Snail在肾癌的侵袭和转移中起重要作用，沉默该基因可能是肾癌潜在的治疗靶点。核因子-κB配体受体激活物(RANKL)及其受体--核因子-κB受体激活物(RANK)在破骨细胞发生中起关键作用，RANKL蛋白表达水平与原发肿瘤分期和远处转移呈正相关。RANKL和RANK在骨和其他器官的转移性肾细胞癌中有表达，提示它们在骨和其他器官的转移中起作用。重组RANKL蛋白可促进肾癌细胞系Caki-1的体外迁移，而重组OPG蛋白可抑制这种促进迁移的作用。这些结果表明RANKL-RANK-OPG系统不仅参与肾细胞癌的骨转移，而且还通过刺激癌细胞的迁移而参与向其他器官的转移。

项目成果

転移性腎癌治療の現状と将来展望

转移性肾癌治疗现状及未来展望

• 发表时间: 2009
• 作者: Takagawa R;Akimoto K;Ichikawa Y;Akiyama H;Kojima Y;Ishiguro H;Inayama Y;Aoki I;Kunisaki C;Endo I;Nagashima Y;Ohno S;大家基嗣
• 通讯作者: 大家基嗣

High nuclear grade has strong prognostic significance in patients with pathologic T1a renal cell carcinoma

高核分级对病理性 T1a 肾细胞癌患者具有很强的预后意义

• 发表时间: 2012
• 作者: Suzuki K;Oya M;et al.
• 通讯作者: et al.

Activation of the aryl hydrocarbon receptor is associated with cigarette smoke, poor prognosis and cancer cell invasion in renal cell carcinoma.

芳烃受体的激活与肾细胞癌中的香烟烟雾、不良预后和癌细胞侵袭有关。

• 发表时间: 2010
• 作者: Ishida M.;Mikami S.;Kosaka T.;Kono H.;Kikuchi E.;Nagata H.;Miyajima A.;Nakagawa K.;Mukai M.;Okada Y.;Oya M.
• 通讯作者: Oya M.

Increased RANKL expression is related to tumour migration and metastasis of renal cell carcinomas

• DOI: 10.1002/path.2567
• 发表时间: 2009-08-01
• 期刊: JOURNAL OF PATHOLOGY
• 影响因子: 7.3
• 作者: Mikami, Shuji;Katsube, Ken-ichi;Okada, Yasunori
• 通讯作者: Okada, Yasunori

Preoperative prognostic nomogram(probabilitytable)for renal cell carcinoma based on TNM classifiration

基于TNM分类的肾细胞癌术前预后列线图（概率）

• 发表时间: 2009
• 期刊: J Urol 181(2)
• 作者: Kanao K;et al
• 通讯作者: et al