A study for mechanism of lymphatic metastasis with human gastric cancer cell line

人胃癌细胞系淋巴转移机制的研究

• 批准号: 10671202
• 负责人: DENNO Ryuichi
• 金额: $ 1.34万
• 依托单位: SAPPORO MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671202/
• 关键词: AZ521; peritoneal metastasis; lymphatic metastasis; integrins; CD44; human gastric cell line; ヒト胃癌細胞株AZ521; ヒト膵癌細胞株HPC-3; 血管新生抑制剤; TNP-470; 腹膜播腫; 肝転移; 高肝転移株AZ-H5G; 高リンパ節転移株AZ-L5G

Though lymph node metastasis is very often encountered in patients with gastric cancer, the biological mechanism of lymph node metastasis is not clarified well, compared with hematogenous and peritoneal metastasis. The animal model of lymph node metastasis is rarely established and reported. We have already established highly liver metastatic mice model, AZ-H7d and peritoneal metastatic model, AZ-P7a, from the parental AZ-521 lines with a low potential of metastasis and investigated the mechanisms of these two types of metastasis. Our results suggested that enhanced expression of VEGF and α3-integrin in hematogenous metastasis, enhanced motile activity and α5-, α v β 5-integrins in peritoneal dissemination might play an important role in gastric cancer. At the basis of these experiments, we established novel mice model with high potential of lymph node metastasis, designated as AZ-L5G.In comparison with AZ-521, we investigated the biology implicated the development of lymph node metastasis. Then the entity that makes the biological differences of lymph node metastasis and hematogenous and/or peritoneal metastasis was investigated compared with AZ-H7d and AZ-P7a. Moreover, recent development of molecular biology revealed that a variety of genes were concerned with the cancer metastasis at their each steps. Using cDNA macroarray and DNA chip technologies, the relative mRNA levels of genes expressed in AZ-521 and AZ-L5G cell lines are identified. Moreover, we perform global analysis on different gene expression of AZ-521, AZ-H7d, AZ-P7a and AZ-L5G.This unique, in vivo model cell line might be highly useful to study the biology of metastasis of gastric cancer and our results lead to the development of new therapeutic modalities against human gastric cancer.

虽然胃癌患者经常发生淋巴结转移，但与血行转移和腹膜转移相比，淋巴结转移的生物学机制尚不清楚。淋巴结转移动物模型的建立和报道很少。我们已经从低转移潜力的亲本AZ-521系建立了高肝转移小鼠模型AZ-H7d和腹腔转移小鼠模型AZ-P7a，并研究了这两种转移的机制。提示VEGF和α3-整合素在胃癌血液转移中的表达增强，运动活性的增强以及α5-、α v β 5-整合素在胃癌腹膜传播中的表达增强可能在胃癌发生过程中起重要作用。在此基础上，我们建立了具有高淋巴结转移潜力的新型小鼠模型，命名为AZ-L5G。与AZ-521相比，我们研究了与淋巴结转移发生有关的生物学机制。然后与AZ-H7d和AZ-P7a比较，探讨导致淋巴结转移和血液及/或腹膜转移的生物学差异的实体。此外，近年来分子生物学的发展表明，多种基因参与了肿瘤转移的各个阶段。利用cDNA macroarray和DNA芯片技术，对AZ-521和AZ-L5G细胞系中表达基因的相对mRNA水平进行了鉴定。此外，我们对AZ-521、AZ-H7d、AZ-P7a和AZ-L5G的不同基因表达进行了全球分析。这种独特的体内模型细胞系可能对研究胃癌转移生物学具有重要意义，我们的研究结果将导致新的治疗方法的发展。

项目成果

Nishimori H., et al.: "A Novel Experimental Mouse Model of Peritoneal Dissemination of Human Gastric Cancer Cells. Different Mechanisms in Peritoneal Dissemination and Hematogenous Metastasis."Jpn J Cancer Res. 91. 715-722 (2000)

Nishimori H.等人：“人类胃癌细胞腹膜播散的新型实验小鼠模型。腹膜播散和血行转移的不同机制。”Jpn J Cancer Res。

Yamaguchi K., et al.: "Establishment and Characterization of a Human Gastric Carcinoma Cell Line that is Highly Metastatic to Lymph Nodes."J Exp Clin Cancer Res. 19. 113-120 (2000)

Yamaguchi K. 等人：“高度转移至淋巴结的人胃癌细胞系的建立和表征。”J Exp Clin Cancer Res。

Shishido T.,Yasoshima T., et al.: "Establishment and characterization of human pancreatic carcinoma lines with a high metastatic potential in the liver of nude mice."Surg Today. 29. 519-529 (1999)

Shishido T.、Yasoshima T. 等人：“在裸鼠肝脏中具有高转移潜力的人胰腺癌细胞系的建立和表征。”Surg Today。

Takayuki Shishido, Takahiro Yasoshima, Koichi Hirata, Ryuichi Denno, Mitsuhiro Mukaiya, Hideki Ura, Koji Yamaguchi, Satoru Kawaguchi, Noriyuki Sato.: "Establishment and characterization of human pancreatic carcinoma lines with a high metastatic potential

Takayuki Shishido、Takahiro Yasoshima、Koichi Hirata、Ryuichi Denno、Mitsuhiro Mukaiya、Hideki Ura、Koji Yamaguchi、Satoru Kawaguchi、Noriyuki Sato.：“具有高转移潜力的人类胰腺癌系的建立和表征

Hidefumi Nishimori, Takahiro Yasoshima, Ryuichi Denno, Takayuki Shishido, Fumitake Hata, Yojiro Okada, Hideki Ura, Koji Yamaguchi, Hiroshi Isomura, Noriyuki Sato, and Koichi Hirata.: "A Novel Experimental Mouse Model of Peritoneal Dissemination of Human G

Hidefumi Nishimori、Takahiro Yasoshima、Ryuichi Denno、Takayuki Shishido、Fumitake Hata、Yojiro Okada、Hideki Ura、Koji Yamaguchi、Hiroshi Isomura、Noriyuki Sato 和 Koichi Hirata。：“人类 G 腹膜传播的新型实验小鼠模型