Invasive and metastatic mechanisms of pancreatic cancer cells: the role of Glial Cell Line-Derived Neurotrophic Factor (GDNF), integrins, and NF-KappaB

胰腺癌细胞的侵袭和转移机制：胶质细胞系衍生神经营养因子 (GDNF)、整合素和 NF-KappaB 的作用

• 批准号: 15591425
• 负责人: FUNAHASHI Hitoshi
• 金额: $ 2.24万
• 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 (C)
• 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-15591425/
• 关键词: GDNF; integrin; NF-KappaB; pancreatic cancer; invasion

Perineural invasion is a prominent clinical feature of pancreatic cancer which difficulty in curative resection. The invasion system forms by multiple steps, but it has not cleared yet. In this study, we investigated the alteration of invasive ability by glial-cell-line-derived neurotrophic factor (GDNF) and the relationship between GDNF, integrin, and NF-kappaB.We used four human pancreatic cancer cells. We confirmed to express the receptors for GDNF. In the invasion assay, all human pancreatic cancer cells stimulated by GDNF increased the invasive ability for Extra Cellular Matrix. The invasive ability was inhibited by anti-receptors antibodies. The integrin subunits expressed in the all cell lines confirmed by the flow-cytometric analysis. In the cellular enzyme-linked immunosorbent assay, the integrin subunit of all cells expressed strongly under stimulating by GDNF and they were inhibited by anti-NF-kB antibody. NF-kappaB moving into the nuclear was enhanced in the all cells stimulated by GDNF. Similarly, after blocking the NF-kappaB, all cell lines showed a decreased ability to invade through the ECM proteins. In the all pancreatic cancer cells, the invasive ability appeared to increase under stimulating by GDNF and the signal of GDNF is transmitted through NF-kappaB.We conclude that GDNF, NF-kappaB and integrins have very important role for the invasive system of pancreatic cancer cells.

神经周围浸润是胰腺癌的一个突出临床特征，手术切除困难。入侵系统是多步骤形成的，但尚未完全清除。在这项研究中，我们研究了胶质细胞系源性神经营养因子（GDNF）的侵袭能力的改变和GDNF，整合素和NF-κ B之间的关系。我们使用了四个人胰腺癌细胞。我们证实了GDNF受体的表达。在侵袭实验中，GDNF刺激的所有人胰腺癌细胞都增加了细胞外基质的侵袭能力。抗受体抗体可抑制其侵袭能力。流式细胞仪分析证实了整合素亚基在所有细胞系中的表达。在细胞酶联免疫吸附试验中，所有细胞的整合素亚基在GDNF刺激下均呈强表达，并可被抗NF-κ B抗体抑制。在GDNF刺激下，所有细胞的NF-κ B向核内移动均增强。类似地，在阻断NF-κ B后，所有细胞系显示出通过ECM蛋白侵袭的能力降低。在所有的胰腺癌细胞中，GDNF的刺激均使胰腺癌细胞的侵袭能力增强，并且GDNF的信号通过NF-κ B传递。因此，GDNF、NF-κ B和整合素在胰腺癌细胞的侵袭系统中起着重要的作用。

项目成果

Tumor malignancy and gene expression analysis.

肿瘤恶性肿瘤和基因表达分析。

• 发表时间: 2003
• 期刊: Surgery Frontier 10
• 作者: Hasegawa;T.;Funahashi H;Funahashi H;Funahashi H;Sawai H;Tanaka M;Funahashi H;Sawai H;Matsuo Y;Takahashi H;Funahashi H;Takahashi H;Funahashi H;Sawai H;Sawai H;Sawai H;Funahashi H;Manabe T;Manabe T;Funahashi H;Sawai H;Sawai H
• 通讯作者: Sawai H

Clinicopathologic study of intraductal papillaly-mucinous tumours and mucinous cystic tumors of the pancreas.

胰腺导管内乳头状粘液性肿瘤和粘液性囊性肿瘤的临床病理学研究。

• 期刊: Hepato-Gastroenterology (in press)
• 作者: Hasegawa;T.;Funahashi H;Funahashi H;Funahashi H;Sawai H;Tanaka M;Funahashi H;Sawai H;Matsuo Y;Takahashi H;Funahashi H;Takahashi H;Funahashi H;Sawai H;Sawai H;Sawai H;Funahashi H;Manabe T;Manabe T;Funahashi H;Sawai H;Sawai H;Sawai H;Sawai H;Sawai H;Funahashi H;Funahashi H;Funahashi H;Sawai H;Tanaka M;Funahashi H;Funahashi H;Funahashi H;Sawai H;Tanaka M
• 通讯作者: Tanaka M

Effect of galanin on plasma glucose, insulin and pancreatic glucagon in dogs

• DOI: 10.1177/147323000303100209
• 发表时间: 2003-03-01
• 期刊: JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
• 影响因子: 1.6
• 作者: Manabe, T;Okada, Y;Yoshimura, T
• 通讯作者: Yoshimura, T

The role of glial cell line-derived neurotrophic factor (GDNF) and integrins for invasion and metastasis in human pancreatic cancer cells

• DOI: 10.1002/jso.20277
• 发表时间: 2005-07-01
• 期刊: JOURNAL OF SURGICAL ONCOLOGY
• 影响因子: 2.5
• 作者: Funahashi, H;Okada, Y;Manabe, T
• 通讯作者: Manabe, T

Glial cell line-derived neurotrophic factor enhances nuclear factor-KB activity and invasive potential in human pancreatic cancer cells

胶质细胞系源性神经营养因子增强人胰腺癌细胞的核因子-KB 活性和侵袭潜力

• 期刊: Pancreas 27
• 作者: Kitamura T;Kometani K;Hashida H;Matsunaga A;Miyoshi H;Hosogi H;Aoki M;Oshima M;Hattori M;Takabayashi A;Minato N;Taketo MM.;Yoichi Matsuo;Hiroki Takahashi
• 通讯作者: Hiroki Takahashi