L1CAM/CD24/heparanase信号轴调控恶性胶质瘤发生和侵袭转移机制研究

Glioblastoma is the most common primary central nervous system tumor, which has poorest prognosis in the solid tumors. The previous studies indicated that the highly expression levels of L1CAM, CD24, and heparanase (HPA) in glioblastoma, suggesting that these the expression levels of three proteins might be associated with the malignancy and prognosis in the patients with glioblastoma. We have found that L1CAM, CD24, and heparanase might compose the complex, indicating that L1/CD24/HPA axis might play an important role in glioma tumorigenesis and invasion, and the inhibition of L1/CD24/HPA axis probably increase the prognosis of the patients with glioblastoma. In this study, we will perform mass spectrum, Co-IP, molecular and cellular technologies, as well as animal model to investigate the molecular mechanisms of the functions of L1/CD24/HPA axis in glioma tumorigenesis and invasion, and identify the specific inhibitor for the L1/CD24/HPA axis. The clarification of the functions of L1/CD24/HPA axis will extend our understanding for the glioma tumorigenesis and invasion, and will be helpful for the improvement of the anti-tumor clinical therapeutic strategy.

恶性胶质瘤是目前最为常见的原发性中枢神经系统肿瘤，在所有实体瘤中其预后是最低的。已有研究发现神经粘附分子L1、CD24和类肝素酶在恶性胶质瘤组织中异常高表达，提示这几种蛋白的表达水平可能与胶质瘤预后和恶性程度相关。本项目前期研究结果发现L1、CD24和类肝素酶可以组成L1/CD24/HPA蛋白质复合体，因此我们推测L1/CD24/HPA信号轴可能对恶性胶质瘤发生和侵袭转移发挥生物学功能，对L1/CD24/HPA信号轴的特异性抑制可望提高胶质瘤患者的预后。本项目拟利用蛋白质谱、Co-IP、分子及生物化学技术、基因敲除小鼠、移植瘤模型等，研究L1/CD24/HPA信号轴对恶性胶质瘤发生和侵袭转移的调控机制，并筛选出特异性抑制性肽段。对这一新机制的阐明，将有助于我们深入理解恶性胶质瘤的发生和侵袭转移的分子机制，并为以L1/CD24/HPA信号轴为靶点的肿瘤临床诊断与治疗提供理论依据。

恶性胶质瘤是目前最为常见的原发性中枢神经系统肿瘤，在所有实体瘤中其预后是最低的。已有研究发现神经粘附分子L1、CD24和类肝素酶在恶性胶质瘤组织中异常高表达，提示这几种蛋白的表达水平可能与胶质瘤预后和恶性程度相关。本项目前期研究结果发现L1、CD24和类肝素酶可以组成L1/CD24/HPA蛋白质复合体，因此我们推测L1/CD24/HPA信号轴可能对恶性胶质瘤发生和侵袭转移发挥生物学功能，对L1/CD24/HPA信号轴的特异性抑制可望提高胶质瘤患者的预后。本项目拟利用蛋白质谱、Co-IP、分子及生物化学技术、基因敲除小鼠、移植瘤模型等，研究L1/CD24/HPA信号轴对恶性胶质瘤发生和侵袭转移的调控机制，并筛选出特异性抑制性肽段。对这一新机制的阐明，将有助于我们深入理解恶性胶质瘤的发生和侵袭转移的分子机制，并为以L1/CD24/HPA信号轴为靶点的肿瘤临床诊断与治疗提供理论依据。