The role of galectin-3 in human renal cell cancer cells

Galectin-3在人肾细胞癌细胞中的作用

• 批准号: 16591599
• 负责人: KANAYAMA Hiro-omi
• 金额: $ 1.79万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591599/
• 关键词: renal cell carcinoma; Apoptosis; Galectin-3; CD8 positive T cells; ガレクチン-3; CTL

Galectin-3 is a member of the galectin gene family that is expressed at elevated levels in a variety of neoplastic cell types and has been associated with cell growth, cellular adhesion process, cell proliferation, transformation, metastasis, and apoptosis. We studied the expression of galecin-3 in renal cell carcinoma cell lines and human renal cell carcinoma tissues by RT-PCR and western blot analysis, and investigated the clinical significance and the possibility as a tumor marker. We also investigated its effect on T cell or NK cell activation. The expression of galectin-3 was identified in every renal cell carcinoma cell line we employed and was significantly higher in human renal cell carcinoma tissues than normal kidney tissues. Especially in the case with metastasis, the expression ratio was significantly high (p=0.035), which suggested that ratio could become prognostic factor of metastasis. We extracted CD8 positive T cells from human renal cell carcinoma tissues and investigated the effect of galectin-3 induced apoptosis in the cells by flow cytometry. Galectin-3 significantly induced apoptosis (p=0.039) by binding to the CD8 positive T cells, from which we concluded that galectin-3 might be involved in what is called ‘escape' from immune system of renal cell carcinoma. We have also constructed mice RCC models and metastasis models by employing Renca cells (positive and negative galectin-3 expression) and investigated anti-angiogenesis and anti-tumor effect. These results will be published shortly. To clarify the role of galectin-3 in angiogenesis or apoptosis may lead to understanding mechanism of resistance of renal cell carcinoma to various kinds of therapies. In future we plan to expand these achievements into gene therapy for renal cell carcinoma.

半乳糖凝集素-3是半乳糖凝集素基因家族的一员，在多种肿瘤细胞类型中表达水平升高，并与细胞生长、细胞粘附过程、细胞增殖、转化、转移和凋亡有关。我们采用RT-PCR和western blot方法研究半乳糖球蛋白-3在肾细胞癌细胞株和人肾细胞癌组织中的表达，探讨其临床意义和作为肿瘤标志物的可能性。我们还研究了它对T细胞或NK细胞活化的影响。半乳糖凝集素-3在我们研究的所有肾细胞癌细胞系中均有表达，且在人肾细胞癌组织中的表达明显高于正常肾组织。特别是在有转移的病例中，表达比显著增高（p=0.035），提示该比值可能成为转移的预后因素。我们从人肾细胞癌组织中提取CD8阳性T细胞，用流式细胞术研究半凝集素-3诱导细胞凋亡的作用。半乳糖凝集素-3通过与CD8阳性T细胞结合显著诱导细胞凋亡（p=0.039），由此我们得出结论，半乳糖凝集素-3可能参与了所谓的肾细胞癌免疫系统的“逃逸”。我们还利用Renca细胞（半凝集素-3阳性和阴性表达）构建了小鼠RCC模型和转移模型，并研究了其抗血管生成和抗肿瘤作用。这些结果将很快公布。阐明半乳糖凝集素-3在血管生成或细胞凋亡中的作用，有助于了解肾细胞癌对各种治疗的耐药机制。未来我们计划将这些成果扩展到肾细胞癌的基因治疗中。

项目成果

A Molecular Classification of Papillary Renal Cell Carcinoma

• DOI: 10.1016/s0084-4071(08)70309-9
• 发表时间: 2006-12
• 期刊: Yearbook of Urology
• 作者: D. Ornstein

Nitrite-derived nitric oxide formation following ischemia-reperfusion injury in kidney

肾脏缺血再灌注损伤后亚硝酸盐衍生的一氧化氮的形成

• 发表时间: 2005
• 期刊: American Journal of Physiology, Renal Physiology 288・1
• 作者: 木村 晋也(筆頭);湯浅 健(5番目);湯浅 健;湯浅 健(金倉 譲編著);Essam Elsamman;Oka N;Hirofumi Izaki;Manabu Sakaki;Essam Elsamman;Tomoharu Fukumori;Hirofumi Izaki;Essam Elsamman;Essam Elsamman;Oka N;Hirofumi Izaki;Manabu Sakaki;Essam Elsamman;Tomoharu Fukumori;Essam Elsamman;Essam Elsamman;Fukumori T;Oka N;Yang XJ;Shimura T;Oka N;Shimura T;Yang XJ;Takahashi M;Inoue Y;Takahashi M;Okamoto M
• 通讯作者: Okamoto M

Characteristics of Patients with Prostate Cancer Who Have Inrtially been Treated by Hormene Therapy in Japan : J-CaP Surveillance

日本已接受激素治疗的前列腺癌患者的特征：J-CaP 监测

• 发表时间: 2004
• 期刊: Japanese Journal of Clinical Oncology 34・6
• 作者: 古賀 成彦;金武 洋;他;Yokomizo A;Debes JD;Yasui K;Hayashi H;Tretiakova MS;Sugimura J;Furga KA;Akaza H
• 通讯作者: Akaza H

Role of the vitamin D receptor in FGF23 action on phosphate metabolism

• DOI: 10.1042/bj20041799
• 发表时间: 2005-08-15
• 期刊: BIOCHEMICAL JOURNAL
• 影响因子: 4.1
• 作者: Inoue, Y;Segawa, H;Miyamoto, K
• 通讯作者: Miyamoto, K

Garectin-3 regulates mitochondrial stability and anti-apoptosis function in response to anti-cancer drugs in prostate cancer

Garectin-3 调节线粒体稳定性和抗凋亡功能以响应前列腺癌的抗癌药物

• 发表时间: 2006
• 期刊: Cancer Research 66
• 作者: 木村 晋也(筆頭);湯浅 健(5番目);湯浅 健;湯浅 健(金倉 譲編著);Essam Elsamman;Oka N;Hirofumi Izaki;Manabu Sakaki;Essam Elsamman;Tomoharu Fukumori;Hirofumi Izaki;Essam Elsamman;Essam Elsamman;Oka N;Hirofumi Izaki;Manabu Sakaki;Essam Elsamman;Tomoharu Fukumori;Essam Elsamman;Essam Elsamman;Fukumori T
• 通讯作者: Fukumori T