Clarification of Nerve Invasion System in Pancreatic Cancer

胰腺癌神经侵犯系统的阐明

• 批准号: 13470258
• 负责人: MANABE Tadao
• 金额: $ 9.09万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470258/
• 关键词: Pancreatic; Nerve invasion; GDNF; RET; Integrin; Tyrosine kinase

We report the results that we acquired till now as follows.1.The expression of GDNF and RET in the intra-and extra-pancreatic nerve plexus was observed by immunohistochemical analysis in resected specimens. It was also proved that pancreatic cancer cells and peri-pancreatic tissues excrete GDNF.2.The role of NF-κB in signaling pathway via GDNF-RET was investigated.(1)MG-132, proteasome inhibior, inhibited the proliferation of pancreatic cancer cells in dose-dependent manner.(2)The invasion cell number and the NF-κB activity were increased by GDNF stimulation. But in the presence of MG132 or I-κB activity were significantly suppressed and remained suppressed after GDNF stimulation.(3)GDNF upregulates the expression and enzymatic activity of MMP-9, and this may promote pancreatic cancer invasion to the extracellular matrixes.

本研究取得的结果如下：1.应用免疫组织化学方法观察GDNF和RET在胰腺内、外神经丛中的表达。胰腺癌细胞和胰腺周围组织中均有GDNF的分泌。2.探讨NF-κB在GDNF-RET信号通路中的作用。（1）蛋白酶体抑制剂MG-132对胰腺癌细胞的增殖有明显的抑制作用，且呈剂量依赖性。（2）GDNF刺激后，侵袭细胞数增加，NF-κB活性增强。但在MG 132或I-κB活性的存在下，显著抑制，并在GDNF刺激后保持抑制。（3）GDNF上调MMP-9的表达和酶活性，可能促进胰腺癌细胞对细胞外基质的侵袭。

项目成果

沢井 博純: "癌転移-基礎と臨床アップデート-膵癌の転移・浸潤に対するIL-1αの影響(Interleukin-1α enhances integrin expression and metastatic and invasive behavior of pancreatic cancer)"日本臨床. 61. 607-611 (2003)

Hirozumi Sawai：“癌症转移 - 基础知识和临床更新 - IL-1α 对胰腺癌转移和侵袭的影响（白细胞介素 1α 增强胰腺癌的整合素表达和转移和侵袭行为）”日本临床 61. 607-611（ 2003）

沢井 博純: "Tumor malignancy and gene expression analysis"Surgery Frontier. 10. 33-38 (2003)

Hirozumi Sawai：《肿瘤恶性与基因表达分析》Surgery Frontier. 10. 33-38 (2003)。

Hirozumi Sawai: "Expression and prognostic roles of integrins and interleukin-1 receptor type I in patients with ductal adenocarcinoma of the pancreas"Digestive Diseases & Sciences. 45. 1248-1250 (2003)

Hirozumi Sawai：“整合素和 I 型白细胞介素 1 受体在胰腺导管腺癌患者中的表达和预后作用”消化系统疾病

Hirozumi Sawai: "Tumor malignancy and gene expression analysis"Surgery Frontier. 10. 22-28 (2003)

Hirozumi Sawai：《肿瘤恶性与基因表达分析》外科前沿。

Hiroki Takahashi: "Glial cell line-derived neurotrophic factor (GDNF) enhances nuclear factor-κB activity and invasive potential in human pancreatic cancer cells."Pancreas. (in press). (2004)

Hiroki Takahashi：“胶质细胞系衍生的神经营养因子 (GDNF) 增强人类胰腺癌细胞的核因子-κB 活性和侵袭潜力。”胰腺（2004 年出版）。