Invasion mechanism of Pancreatic cells : the relationship Glial cell line-derived neurotrophic factor and integrin

胰腺细胞的侵袭机制：胶质细胞源性神经营养因子与整合素的关系

• 批准号: 13671325
• 负责人: TAKEYAMA Hiromitsu
• 金额: $ 1.86万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671325/
• 关键词: Pancreatic; neural invasion; GDNF; RET; GFRalpha-1; integrin; GFRalpha1; GFR21

Prineural invasion is a prominent clinical feature of pancreatic cancer. The invasion system forms by multiple steps, but it has not cleared yet. We pay attention to the integrins and investigated its expression and alteration by GDNF. In this study, we use four human pancreatic cancer cell lines which were all found to express the receptor RET and GFRalpha-1 for GDNF. In the invasion assay, all human pancreatic cancer cell lines stimulated by GDNF increased the invasive ability for ECMs. In the adhesion assay, they increased the adhesive ability for ECMs. All pancreatic cancer cell lines stimulated by GDNF, their adhesive and the invasive ability in inhibited by anti-RET antibody, anti-GFRalpha-1 antibody and anti-betal antibody. In the flow-cytometric analysis, the integrin subunit alpha2, alpha3, alpha5, alpha6 and betal expressed in the all pancreatic carcinoma cell lines. In the cellular enzyme-linked immunosorbent assay, the integrin subunit expressed strongly under stimulating by GDNF. In the all pancreatic cancer cell lines, the expression of integrin subunit, the invasive ability and the adhesive ability appeare to increase under stimulating by GDNF. NF-kappaB was enhanced in the all pancreatic tumor cells stimulated by GDNF. We conclude that GDNF and integrin have very important role for the neural' invasive system of pancreatic cancer cells. We suggest that the control of the receptor or integrin makes new therapy.

神经侵袭是胰腺癌的一个显著临床特征。入侵系统是分步骤形成的，但尚未清除。我们关注整合素，并用胶质细胞源性神经营养因子研究其表达和变化。在这项研究中，我们使用了四个都被发现表达GDNF受体RET和GFRα-1的人胰腺癌细胞株。在侵袭实验中，GDNF刺激的所有人胰腺癌细胞株对ECM的侵袭能力均增强。在黏附实验中，它们提高了细胞外基质的黏附能力。抗RET抗体、抗GFRα-1抗体和抗β1抗体均能抑制GDNF刺激的胰腺癌细胞株的黏附和侵袭能力。在流式细胞仪分析中，整合素亚单位α2、α3、α5、α6和β1在所有胰腺癌细胞株中均有表达。在细胞酶联免疫吸附实验中，整合素亚单位在GDNF刺激下表达增强。在ALL胰腺癌细胞系中，在GDNF刺激下，整合素亚单位的表达、侵袭能力和黏附能力均出现增加。GDNF刺激的ALL胰腺癌细胞中，NF-kappaB表达增强。结论：GDNF和整合素在胰腺癌细胞的神经侵袭系统中具有重要作用。我们建议通过对受体或整合素的控制来创造新的治疗方法。

项目成果

HITOSHI FUNAHASHI, HIROMITSU TAKEYAMA, HIROZUMI SAWAI, AKIYOSHI FURUTA, MIKINORI SATO, YUJI OKADA, TESUSHI HAYAKAWA, MORITSUGU TANAKA, and TADAO MANABE: "Alteration of Integrin Expression by Grial Cell Line-Derived Neurotrophic Factor (GDNF) in Human Panc

HITOSHI FUNAHASHI、HIROMITSU TAKEYAMA、HIROZUMI SAWAI、AKIYOSHI FURUTA、MIKINORI SATO、YUJI OKADA、TESUSHI HAYAKAWA、MORITSUGU TANAKA 和 TADAO MANABE：“人胰腺中胶质细胞系衍生神经营养因子 (GDNF) 改变整合素表达

TADAO MANABE: "Current aspects of the pathophysiology of acute pancreatitis and therapeutic effects of an inflammatory cell infiltration inhibitor"Journal of Gastroenterology. 38. 305-307 (2003)

TADAO MANABE：“急性胰腺炎病理生理学的当前方面和炎症细胞浸润抑制剂的治疗效果”胃肠病学杂志。

TADAO MANABE: "Current aspects of the pathophysiology of acute pancreatitis and therapeutic effects of an inflammatory cell infiltration inhibitor"Journal of Gastroenterology. 38(3). 305-307 (2003)

TADAO MANABE：“急性胰腺炎病理生理学的当前方面和炎症细胞浸润抑制剂的治疗效果”胃肠病学杂志。

HIRDZUMI SAWAI, HITOSHI FUNAHASHI, and TADAO MANABE: "Tumor malignancy and gene expression analysis"Surgery Frontier. 10(1). 33-38 (2003)

HIRDZUMI SAWAI、HITOSHI FUNAHASHI 和 TADAO MANABE：“肿瘤恶性肿瘤与基因表达分析”外科前沿。

HITOSHI FUNAHASHI: "Alteration of Integrin Expression by Grial Cell Line-Derived Neurotrophic Factor (GDNF) in Human Pancreatic Cancer Cells"Pancreas. (in press).

HITOSHI FUNAHASHI：“人胰腺癌细胞中胶质细胞系衍生的神经营养因子（GDNF）对整合素表达的改变”胰腺。