Tumor control mechanism of galactoside-binding lectin in metastasis of urogenital cancer

半乳糖苷结合凝集素在泌尿生殖系统肿瘤转移中的肿瘤控制机制

• 批准号: 17591681
• 负责人: FUKUMORI Tomoharu
• 金额: $ 2.24万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591681/
• 关键词: urogenital cancer; apoptosis; galectin; metastasis; 血管新生

Galectin-3, a member of the β-galactoside binding protein family found in the intracellular and extracellular milieu, has overexpressed in a variety of cancer cells and has been shown to be correlated with tumor progression and metastasis through the regulation of tumor proliferation, angiogenesis, and apoptosis.Concerning the prostate cancer, after treatment with 25 μM CDDP for 48 hours, 66.3% of control LNCap cells which are garectiin-3 negative prostate cancer cell line showed DNA fragmentation, whereas only 2.9% of galectin-3 expressing LNCap cells were apoptotic. In the exposure with 300 μM etoposide for 48 hours, 48.3% of control LNCap cells were apoptotic, whereas only 15.4% of galectin-3 expressing LNCap were apoptotic. Intracellular galectin-3 inhibited mitochondrial damage after translocation from nuclei to cytoplasm, resulting inhibition of cytochrome c release and caspase-3 activation. Galectin-3 inhibited anticancer drug-induced apoptosis in the result of regulation of mitochondrial integrity, cytochrome c release, and caspase-3 activation.Recent our microarray studies have revealed garectin-3 overexpresses in human renal cell carcinoma (RCC). The expression level of galectin-3 in RCC obtained from nephrectomy was significantly higher than that in renal parenchyma obtained from same samples. After treatment with supernatant of garectin-3 expressing cells for 12 hours, approximately 45% of CD8+ T-cells were apoptotic, whereas in galectin-3 reduced cells by siRNA, only 15-18% of the cells were apoptotic. These result indicates that galectin-3 is highly expressed in RCC and extracellular garectin-3 induces apoptosis of CD8+ T-cells.These results suggest that galectin-3 regulated anticancer drug-induced apoptosis in prostate cancer and anti-cancer immune suppression in RCC. Taken together, it is suggested that galectin-3 is one of the target proteins for cancer chemotherapy in prostate cancer and immune escape of RCC.

Galectin-3是β-半乳糖苷结合蛋白家族的成员，存在于细胞内和细胞外环境中，在多种癌细胞中过表达，并已显示通过调节肿瘤增殖、血管生成和凋亡与肿瘤进展和转移相关。关于前列腺癌，用25 μM CDDP处理48小时后，66.3%的对照LNCap细胞（其为胃泌素-3阴性前列腺癌细胞系）显示DNA片段化，而仅2.9%的半乳糖凝集素-3表达LNCap细胞是凋亡的。在用300 μM依托泊苷暴露48小时中，48.3%的对照LNCap细胞凋亡，而仅15.4%的半乳糖凝集素-3表达LNCap细胞凋亡。细胞内半乳糖凝集素-3抑制线粒体损伤后易位从细胞核到细胞质，导致细胞色素c的释放和半胱天冬酶-3激活的抑制。Galectin-3通过调节线粒体的完整性、细胞色素c的释放和caspase-3的激活来抑制抗癌药物诱导的细胞凋亡。Galectin-3在肾癌组织中的表达水平明显高于肾实质组织。在用表达garectin-3的细胞的上清液处理12小时后，约45%的CD 8 + T细胞凋亡，而在通过siRNA减少半乳糖凝集素-3的细胞中，仅15-18%的细胞凋亡。这些结果表明galectin-3在RCC中高表达，并且细胞外galectin-3诱导CD 8 + T细胞凋亡，这些结果表明galectin-3调节抗癌药物诱导的前列腺癌细胞凋亡和RCC中的抗癌免疫抑制。综上所述，半乳糖凝集素-3是前列腺癌化疗和RCC免疫逃逸的靶蛋白之一。

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

Differences in gene expression between noninvasive and invasive transitional cell carcinoma of the human bladder using complementary deoxyribonucleic acid microarray: Preliminary results

• DOI: 10.1016/j.urolonc.2005.07.011
• 发表时间: 2006-03-01
• 期刊: UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
• 影响因子: 2.7
• 作者: Elsamman, E;Fukumori, T;Kanayama, H
• 通讯作者: Kanayama, H

Bilateral adrenal myelolipoma associate with adrenogenical syndrome

双侧肾上腺髓脂肪瘤与肾上腺综合征相关

• 发表时间: 2006
• 期刊: International Journal of Urology 13
• 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
• 通讯作者: Manabu Sakaki

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

a molecular classification of papillary renal cell carsinoma.

乳头状肾细胞癌的分子分类。

• 发表时间: 2005
• 期刊: Cancer Research 65・13
• 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
• 通讯作者: Yang XJ