蛋白聚糖Glypican-6在胰腺癌及其肿瘤组织纤维化发生中的功能机制研究

糖基化磷酯酰肌醇蛋白聚糖（glypican）是硫酸乙酰肝素蛋白聚糖（HSPG）主要家族成员，在肿瘤发生发展中担任关键角色。Glypican-6（GPC-6）是 Glypican家族中一员。我们前期研究发现GPC-6在胰腺癌肿瘤组织相比癌旁组织中有显著高表达。过表达该基因能促进胰腺癌细胞的生长，而沉默该基因子在体内能抑制胰腺癌细胞移植瘤及其组织中纤维化的发生。但GPC-6在胰腺癌及其组织纤维化发生发展中的功能及其相关机制仍然不清楚。本项目将研究 1，GPC-6在胰腺癌细胞生长，侵袭，转移中的功能机制；2，GPC-6在胰腺癌组织纤维化中的功能机制；3， GPC-6诱导的纤维化与胰腺癌细胞生长，侵袭与转移的相关机制；4，在上述研究的基础上，运用胰腺癌耐药株探究GPC-6在胰腺癌肿瘤耐药中的功能机制。本项目的实施将为理解胰腺癌的发生发展机制、新靶标的发现及其精准治疗以及创新药物研究奠定坚实理论基础

Glypican is one main member of heparan sulfate proteoglycans family and play key pivotal role in tumor development. GPC-6 is one of membranes of glypicans. Preliminary study suggested that GPC-6 was highly expressed in pancreatic cancer tissue than that of benign tissue. Overexpressed GPC-6 promoted pancreatic cancer cells growth. Deletion of GPC-6 inhibited xenografted pancreatic cancer cells growth and fibrogenesis. However the mechanism underlying action of GPC-6 in pancreatic carcinogenesis and tumor fibrogenesis is still vague. This project focuses studies of 1) mechanism of GPC-6 in pancreatic cancer cell growth, invasion and metastasis; 2) role of GPC-6 in fibrogensis in pancreatic cancer; 3) the relationship between GPC-6 induced fibrogenesis and pancreatic cancer growth, invasion and metastasis; 4) the role of GPC-6 in pancreatic cancer cells resistance to drug. These studies may provide solid evidences to advance mechanism understanding of GPC-6 in pancreatic cancer development, anti-pancreatic cancer targeting molecule discovery, precise treatment and new drug development by aiming GPC-6.