PDF(Pubmed)
Abstract：
Many nervous proteins are expressed in cancer cells. In this report, we asked whether the synaptic protein neuroligin 1 (NLGN1) was expressed by prostatic and pancreatic carcinomas; in addition, given the tendency of these tumors to interact with nerves, we asked whether NLGN1 played a role in this process. Through immunohistochemistry on human tissue microarrays, we showed that NLGN1 is expressed by prostatic and pancreatic cancer tissues in discrete stages and tumor districts. Next, we performed in vitro and in vivo assays, demonstrating that NLGN1 promotes cancer cell invasion and migration along nerves. Because of the established role of the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) in tumor-nerve interactions, we assessed a potential NLGN1-GDNF cooperation. We found that blocking GDNF activity with a specific antibody completely inhibited NLGN1-induced in vitro cancer cell invasion of nerves. Finally, we demonstrated that, in the presence of NLGN1, GDNF markedly activates cofilin, a cytoskeletal regulatory protein, altering filopodia dynamics. In conclusion, our data further prove the existence of a molecular and functional cross-talk between the nervous system and cancer cells. NLGN1 was shown here to function along one of the most represented neurotrophic factors in the nerve microenvironment, possibly opening new therapeutic avenues.
摘要：
许多神经蛋白在癌细胞中表达。在这份报告中,我们询问突触蛋白neuroligin1（NLGN1）是否在前列腺癌和胰腺癌中表达；此外，考虑到这些肿瘤与神经相互作用的趋势，我们询问NLGN1是否在此过程中发挥作用。通过人体组织微阵列的免疫组织化学，我们发现NLGN1在不同分期和肿瘤区的前列腺和胰腺癌组织中表达。接下来,我们进行了体外和体内试验，证明NLGN1促进癌细胞侵袭和沿神经迁移。由于神经营养因子胶质细胞系源性神经营养因子（GDNF）在肿瘤-神经相互作用中的作用已确立，我们评估了NLGN1-GDNF的潜在合作。我们发现用特异性抗体阻断GDNF活性完全抑制NLGN1诱导的体外癌细胞对神经的侵袭。最后,我们证明了，在NLGN1的存在下，GDNF显着激活cofilin，细胞骨架调节蛋白，改变丝状体动力学。总之,我们的数据进一步证明了神经系统和癌细胞之间存在分子和功能的串扰.NLGN1在这里被证明在神经微环境中沿着最典型的神经营养因子之一起作用,可能会开辟新的治疗途径。
