The role of glial cell line-derived neurotrophic factor (GDNF) and integrins for invasion and metastasis in human pancreatic cancer cells
The role of glial cell line-derived neurotrophic factor (GDNF) and integrins for invasion and metastasis in human pancreatic cancer cells
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DOI：
10.1002/jso.20277
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发表时间：
2005-07-01
影响因子：
2.5
通讯作者：
Manabe, T
中科院分区：
文献类型：
--
作者：
Funahashi, H;Okada, Y;Manabe, T
背景和目标：一般认为胰腺癌的恶性程度取决于浸润和转移的程度。然而，这些因素和机制并不完全清楚。方法：采用逆转录聚合酶链反应（RT-PCR）方法检测胰腺癌细胞株SW 1990和Capan-2中GDNF受体的表达，并与正常胰腺癌细胞株比较。用流式细胞术和细胞酶联免疫吸附试验（CELISA）检测了GDNF对整合素4个亚基表达的影响。粘附和侵袭实验检测整合素表达增加是否影响胰腺癌细胞与ECM蛋白的相互作用。GDNF增强了某些整合素亚基的表达，并增强了它们的粘附和侵袭能力。GDNF受体或整合素β 1亚基的阻断可抑制整合素表达的增强以及粘附和侵袭能力的相关增加。结论：GDNF受体介导的GDNF信号转导增强了整合素的表达，从而强烈影响胰腺癌细胞对ECM蛋白的侵袭和粘附。
Background and Objectives: It is generally accepted that the malignancy of pancreatic cancer is dependent upon the extent of invasion as well as metastasis. However, the factors and mechanisms are incompletely understood. We investigated whether glial cell lined-derived neurotrophic factor (GDNF) enhances the invasive and adhesive behaviors of pancreatic cancer cells by altering of the expression of integrins.Methods: The expression of the GDNF receptor in pancreatic cancer cell lines (SW1990 and Capan-2) was confirmed by RT-PCR. Then we determined the expression 4 integrin subunits and the alteration of their expression by GDNF using flow-cytometric analysis and a cellular enzyme-linked immunosorbent assay (CELISA). Adhesion and invasion assay were performed to investigate whether increased integrin expression affected the interaction between cancer cells and ECM proteins.Results: The GDNF receptor subunits were expressed in pancreatic cancer cells. GDNF enhanced the expression of some of the integrin subunits and increased their adhesive and invasive abilities. The enhanced expression and associated increase in adhesive and invasive abilities were inhibited by blocking the GDNF receptor or the integrin beta 1 subunit.Conclusion: The enhancement of integrin expression by GDNF signaling through the GDNF receptor strongly influences invasion and adhesion to ECM proteins by pancreatic cancer cells.