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

神经外侵是胰腺癌的一个显著临床特征。入侵系统是经过多个步骤形成的，但目前尚未清除。我们关注整合素并研究了其在GDNF作用下的表达和改变。在这项研究中，我们使用了四种人类胰腺癌细胞系，它们都被发现表达GDNF的受体RET和GFRalpha-1。在侵袭实验中，GDNF刺激的所有人胰腺癌细胞系对ecm的侵袭能力均增加。在粘附实验中，它们增加了ecm的粘附能力。所有经GDNF刺激的胰腺癌细胞系，其粘附和侵袭能力均被抗ret抗体、抗gfrα -1抗体和抗β抗体抑制。流式细胞术分析显示，整合素亚基alpha2、alpha3、alpha5、alpha6和betal在所有胰腺癌细胞系中均有表达。在细胞酶联免疫吸附实验中，整合素亚基在GDNF刺激下强烈表达。在所有胰腺癌细胞系中，在GDNF的刺激下，整合素亚基的表达、侵袭能力和粘附能力均出现增强。NF-kappaB在GDNF刺激的所有胰腺肿瘤细胞中均增强。我们认为GDNF和整合素在胰腺癌细胞的神经侵袭系统中具有重要的作用。我们建议通过控制受体或整合素来开发新的治疗方法。

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.