Clarification of control mechanisms for lever metastasis and nerve invasion in pancreatic cancer

阐明胰腺癌杠杆转移和神经侵犯的控制机制

• 批准号: 17591427
• 负责人: TAKAHASHI Hiroki
• 金额: $ 2.05万
• 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: 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-17591427/
• 关键词: GDNF; pancreatic cancer; transcription factor; adhesion molecule; integrin

We previously reported that the neurotrophic factor GDNF has an important role in the invasive capability of pancreatic cancer cells. Furthermore, we confirmed that the integrins have a critical role for invasive and metastatic potential of pancreatic cancer cell lines. The aims of this study was to identify the role of GDNF for pancreatic cancer cell adhesive and invasive capabilities.We report the results that we acquired till now as follows.1. GDNF significantly activated ERK-1/2 and PI3-K signaling pathways, furthermore, the activation of transcription factor NF-kB was observed.2. GDNF significantly enhanced the expression of integrin subunits involved in adhesive and invasive capabilities of pancreatic cancer cells.3. GDNF correlated with the activation of ERK-1/2 signaling pathways in pancreatic cancer cells and these enhancements can be inhibited by MEK-1 inhibitor.4. Invasive potential of pancreatic cancer cells was also regulated by NF-kB activation via GDNF stimulation. Furthermore, NF-kB inhibitor had an important role in the inhibition of neural invasion in human pancreatic cancer cells.In this study, we proved the signaling pathways involved in neural invasion in human pancreatic cancer cells, and our results suggested that the control of these signaling pathways contributes to the improvement of cure rate for pancreatic cancer.

我们以前报道过神经营养因子GDNF在胰腺癌细胞的侵袭能力中起重要作用。此外，我们证实了整合素对胰腺癌细胞系的侵袭和转移潜力具有关键作用。本研究旨在探讨GDNF对胰腺癌细胞粘附和侵袭能力的影响，现将研究结果报道如下：1. GDNF显著激活ERK-1/2和PI 3-K信号通路，并抑制转录因子NF-κ B的激活. GDNF显著增强胰腺癌细胞粘附和侵袭能力相关的整合素亚单位的表达. GDNF与胰腺癌细胞ERK-1/2信号通路的激活相关，并且这种增强作用可被MEK-1抑制.胰腺癌细胞的侵袭潜力也通过GDNF刺激的NF-κ B活化来调节。此外，NF-κ B抑制剂在抑制胰腺癌细胞的神经侵袭中具有重要作用，本研究证实了胰腺癌细胞神经侵袭的信号通路，提示对这些信号通路的调控有助于提高胰腺癌的治愈率。

项目成果

Expression of α_6 integrin subunit is associated with malignancy in gastric gastrointestinal stromal tumors

α_6整合素亚基的表达与胃胃肠道间质瘤的恶性相关

• 发表时间: 2007
• 期刊: Medical Science Monitor 13
• 作者: Takeyama;H
• 通讯作者: H

Integrin-linked kinase activity is associated with interleukin-la-induced progressive behavior of pancreatic cancer and poor patient survival

整合素连接激酶活性与白细胞介素-1α诱导的胰腺癌进展行为和患者较差的生存率相关

• 发表时间: 2006
• 期刊: Oncogene 25
• 作者: Ozaki;K.;Nagasaka;T.;Notohara;K.;Kambara;T.;Takeda;M.;Sasamoto;H.;Jass;J.R.;Tanaka;N.;Matsubara;N.;Hirozumi Sawai;Yu Maki et al.;Hirozumi Sawai
• 通讯作者: Hirozumi Sawai

Activation of focal adhesion kinase enhances the adhesion and invasion of pancreatic cancer cells via extracellular signal-regulated kinase-1/2 signaling pathway activation.

局灶性粘附激酶的激活通过细胞外信号调节的激酶-1/2信号传导途径激活来增强胰腺癌细胞的粘附和侵袭。

• DOI: 10.1186/1476-4598-4-37
• 发表时间: 2005-10-06
• 期刊: MOLECULAR CANCER
• 影响因子: 37.3
• 作者: Sawai, Hirozumi;Okada, Yuji;Funahashi, Hitoshi;Matsuo, Yoichi;Takahashi, Hiroki;Takeyama, Hiromitsu;Manabe, Tadao
• 通讯作者: Manabe, Tadao

Stem Cell Factor/c-kit Receptor Signaling Enhances the Proliferation and Invasion of Colorectal Cancer Cells Through the PI3K/Akt Pathway

• DOI: 10.1007/s10620-007-9759-7
• 发表时间: 2007-04
• 期刊: Digestive Diseases and Sciences
• 影响因子: 3.1
• 作者: Akira Yasuda;H. Sawai;Hiroki Takahashi;N. Ochi;Y. Matsuo;H. Funahashi;Mikinori Sato;Y. Okada;H. Takeyama;T. Manabe

Immunohistochemical analysis of interleukin-1 receptor type I and α_6 integrin subunit in advanced gastrointestinal stromal tumor of the rectum with liver metastasis

晚期直肠胃肠间质瘤肝转移中白细胞介素1受体I型及α_6整合素亚基的免疫组织化学分析

• 发表时间: 2007
• 期刊: Hepatogastroenterology 54 (In press)
• 作者: Sawai;H
• 通讯作者: H