Study of escape mechanism from host immunity by cancer-derived cytokine

癌源细胞因子逃避宿主免疫机制的研究

• 批准号: 15390130
• 负责人: KUNIYASU Hiroki
• 金额: $ 2.75万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390130/
• 关键词: HMGB1; amphoterin; macrophage; apoptosis; AGE; RAGE; colon cancer; アンフォテリン; JNK; 癌免疫

In this research project, the investigator aimed to elucidate the mechanism that cancer cells escape from the host immunity to promote cancer progression. The target of the project is focused on RAGE-HMGB1/amphoterin system, because the investigator already characterized the metastasis-related features of the system. The results of the project showed that HMGB1/amphoterin secreted from cancer cells induces apoptosis by activating RAGE in the macrophages. Colon cancer cases with HMGB1/amphoterin overexpression showed macrophage-negative areas in the cancer tissues. The macrophage depletion is significantly associated with metastasis and poor prognosis of disease.The RAGE-HMGB1/amphoterin system is employed to colon carcinogenesis. In the AOM-induced rat colon cancer model, overexpression of RAGE and secretion of HMGB1/amphoterin are observed from the early stage of epithelial cell transformation. Transplanted tumors of human colon cancer cells in nude mice are suppressed by direct injection of an HMGB1/amphoterin-neutralizing antibody into the tumors accompanied with increase of tumor-associated macrophages.These results overall indicate that the RAGE-HMGB1/amphoterin system plays a pivotal role in colon cancer development, progression, and metastasis by suppression of the host anti-cancer immunity in addition to activation of cancer cell invasion. It suggests that the RAGE-HMGB1/amphoterin system is an important target of cancer treatment.

在这个研究项目中，研究人员旨在阐明癌细胞逃离宿主免疫以促进癌症进展的机制。该项目的目标集中在RAGE-HMGB1/两性蛋白系统上，因为研究人员已经表征了该系统的转移相关特征。该项目的结果表明，癌细胞分泌的HMGB1/两性蛋白通过激活巨噬细胞中的RAGE来诱导细胞凋亡。 HMGB1/两性蛋白过度表达的结肠癌病例在癌症组织中显示出巨噬细胞阴性区域。巨噬细胞耗竭与疾病的转移和不良预后显着相关。RAGE-HMGB1/两性蛋白系统用于结肠癌发生。在AOM诱导的大鼠结肠癌模型中，从上皮细胞转化的早期阶段就观察到RAGE的过度表达和HMGB1/两性蛋白的分泌。通过将HMGB1/两性蛋白中和抗体直接注射到肿瘤中，伴随着肿瘤相关巨噬细胞的增加，裸鼠体内的人结肠癌细胞移植肿瘤得到抑制。这些结果总体表明，RAGE-HMGB1/两性蛋白系统通过抑制宿主在结肠癌的发生、进展和转移中发挥着关键作用。 除了激活癌细胞侵袭之外，还具有抗癌免疫力。这表明RAGE-HMGB1/两性蛋白系统是癌症治疗的重要靶点。

项目成果

Alterations of the Dutt1/Robo1 gene in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats.

N-亚硝基双（2-羟丙基）胺诱导大鼠肺腺癌中 Dutt1/Robo1 基因的改变。

• 发表时间: 2004
• 期刊: Mol Carcinog 40(4)
• 作者: Tsujiuchi T;Kuniyasu H;et al.
• 通讯作者: et al.

Discrepancy between E-cadherin protein expression and morphology in human gastric carcinoma cells.

人胃癌细胞中E-钙粘蛋白表达和形态之间的差异。

• 期刊: Hepato-Gastroenterol (in press)
• 作者: Sasaki T;Kuniyasu H;et al.
• 通讯作者: et al.

Loss of heterozygosity and histone hypoacetylation of the PINX1 gene are associated with reduced expression in gastric carcinoma

• DOI: 10.1038/sj.onc.1207832
• 发表时间: 2005-01-06
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Kondo, T;Oue, N;Yasui, W
• 通讯作者: Yasui, W

Effects of isoliquirithigenin on the development of preneoplastic liver lesions caused by a choline-deficient, L-amino acid-defined diet and on the urinary bladder carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine in rats.

异甘草苷元对大鼠中由缺乏胆碱、L-氨基酸限定饮食引起的癌前肝脏病变的发展以及对 N-丁基-N-(4-羟丁基)亚硝胺引起的膀胱癌发生的影响。

• 发表时间: 2003
• 期刊: J Toxicol Pathol 16(4)
• 作者: Denda A;Kuniyasu H;et al.
• 通讯作者: et al.

Kuniyasu H 他2名: "A role of histone H4 hypoacetylation in vascular endothlial growth factor expression in colon mucosa adjacent to implanted cancer in athymic mice cecum"Pathobiology. 70(6). 348-352 (2003)

Kuniyasu H 和其他 2 人：“组蛋白 H4 低乙酰化对无胸腺小鼠盲肠植入癌附近结肠粘膜血管内皮生长因子表达的作用”病理学 70(6) (2003)。