非经典趋化因子受体CXCR7协同“同胞”受体CXCR4调控胰腺癌趋向性转移及神经浸润的机制研究

项目名称： 非经典趋化因子受体CXCR7协同“同胞”受体CXCR4调控胰腺癌趋向性转移及神经浸润的机制研究

项目编号： No.81502528

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 徐勤鸿

作者单位： 西安交通大学

项目金额： 18万元

中文摘要： 课题组前期研究发现趋化因子CXCL12的浓度梯度能够诱导CXCR4阳性表达的胰腺癌细胞发生特异性趋化转移及神经浸润，而肿瘤微环境中CXCL12的浓度梯度的形成机制尚不清楚。最新研究发现，胚胎形成过程中，细胞表面受体CXCR7通过对CXCL12的清除作用，改变最初均一的细胞外引导信号，产生局部浓度梯度，诱导细胞定向迁移，调控组织器官发育。因此我们推断：在肿瘤转移过程中，高表达CXCR7受体的胰腺癌细胞，通过清除局部CXCL12建立稳定有效的浓度梯度，继而诱导CXCR4阳性的胰腺癌细胞向远处器官形成特异性转移及神经浸润。本研究拟从组织学、细胞学、分子生物学等水平，运用小动物活体成像、荧光素酶报告系统及分子影像学等技术，探究非经典受体CXCR7通过与其“同胞”受体CXCR4的协同作用，调控胰腺癌的趋向性转移和神经浸润的相关机制，继而阐明胰腺癌侵袭转移的发生机理并提供新的潜在治疗靶点。

中文关键词： C11_胰肿瘤；浸润与转移；趋化因子；神经浸润；肿瘤微环境

英文摘要： Previous study of our team found that concentration gradient of chemokine CXCL12 can induce specificity chemotaxis and perineural invasion of CXCR4 positive pancreatic cancer cells, however formation mechanism for the concentration gradient of CXCL12 in tumor microenvironment is still unclear. A new study found that, in the process of embryo formation, cell surface receptor CXCR7 scavenging CXCL12, modulates the original uniformed concentration around the cells, generates local concentration gradient, induces directional migration, and eventually regulates the organ development. So we hypothesize that: Pancreatic cancer cells expressed highly level of CXCR7 scavenge local CXCL12 to establish a stable and effective concentration gradient, which induces the directional metastasis to distant organs and nerve infiltration of CXCR4 positive pancreatic cancer cells. In this study, various methods such as in vivo fluorescence imaging,the fusion protein of CXCR7, CXCR4, CXCL12 combined with luciferase, and other molecular imaging techniques could be applied to confirm that non-canonical chemokine receptor CXCR7 assisting its twins receptor CXCR4 modulates the specific metastasis and neural invasion of pancreatic cancer. It could clarify the mechanism of the metastasis and invasion in pancreatic cancer and help us to find the promising therapeutic target on pancreatic cancer progression.

英文关键词： pancreatic cancer;metastasis and invasion;chemokine;perineural invasion;tumor microenviroment