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THE STUDY FOR REGULATION OF THE DEVELOPMENTAL DYNAMICS OF LYMPHATIC SYSTEMS IN HEAD AND NECK, AND FOR THE ADHESION SYSTEMS OF CANCER CELLS TO LYMPHATIC ENDOTHELIUM

头颈部淋巴系统发育动力学调控及癌细胞与淋巴内皮粘附系统的研究

基本信息

批准号：
14370575
负责人：
YOSHIDA Shigemitsu
金额：
$ 8.9万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2005
项目状态：
已结题

项目摘要

We have been cleared that the human lymphatic endothelium expresses desmoplakin which is a component of desmosome. In this study, the expression of desmosome-associated proteins ; desmoplakins and plakoglobin in plaque, and desmocollins and desmogleins in core was tested on the oral squamous cell carcinoma (OSCC) in the maxillary antrum and tongue. In the results, 1)lymphatic endothelium in cancer tissues expressed desmoplakins, 2)OSCC in lymphatic vessles overexpressed desmoplakins, and 3)OSCC developed a tendency to lose desmosomal core. In the study for the expression of desmosomal proteins on OSCC cell lines ; HSC2,HSC3,HSC4,HO1myu1,HO1N1,Ca.922,SAS,KB, it was observed that 1)all cell lines did not express desmoglein 1 and 2, 2)KB did not express desmoglein 1-3, 3)all cell lines except for Ca.922 did not express desmocollin 1, 4)HSC4,HO1myu1,HO1N1,SAS rarely express desmocollin 2, 5)all cell lines express desmocollin 3, plakoglobin, and desmoplakin 1 and 2, and 6)in HO1myu1,HO1N1,Ca.922, and SAS, desmoplakin expresses at cell-cell contact but in HSC2,HSC3, and HSC4, desmoplakin diffuses intracellularly. The OSCC may bind to lymphatic vessels with surface exposed desmoplakin overexpressed on cells. Furthermore the OSCC cells in both cell lines and tissues having p53 mutant also intracellulaly overexpressed desmoplakin. The over-expression of desmoplakin may be implicated of the p53 mutation. In the cell growth test for the human neonatal lymphatic endothelial cells (HNDLEC), it was showed that HNDLEC could not proliferate without vascular endothelium growth factor (VEGF) and insulin-like growth factor (IGF). The proliferative test of HNDLEC in co-culture with HSC2,HSC3,HSC4,HO1myul,HO1N1,Ca.922,SAS, and KB, it was suggested that the maintenance of cell viability of HNDLEC is longer in co-culture with HSC3, HO1myu1, SAS than in culture without them. Some OSCC may produce the growth factors which need to the lymphatic angiogenesis.

我们已经清楚，人类淋巴管内皮细胞表达桥粒的一个组成部分，桥斑蛋白。在这项研究中，桥粒相关蛋白的表达;桥斑蛋白和斑珠蛋白在斑块，桥芯和桥芯糖蛋白在口腔鳞状细胞癌（OSCC）的上颌窦和舌头进行了测试。结果表明：1）癌组织的淋巴管内皮细胞表达桥粒斑蛋白，2）淋巴管中的OSCC过表达桥粒斑蛋白，3）OSCC有桥粒核心丢失的趋势。研究桥粒蛋白在口腔鳞癌细胞系中的表达; HSC 2、HSC 3、HSC 4、HO 1 myu 1、HO 1 N1、Ca.922、SAS、KB，观察到1）所有细胞系不表达桥粒芯蛋白1和2，2）KB不表达桥粒芯蛋白1-3，3）除Ca.922外的所有细胞系不表达桥粒芯蛋白1，4）HSC 4、HO 1 myu 1、HO 1 N1、SAS很少表达桥粒芯蛋白2，5）所有细胞系均表达桥粒胶原蛋白3、斑珠蛋白和桥粒斑蛋白1和2; 6）在HO 1 myu 1、HO 1 N1、Ca. 922和SAS中，桥粒斑蛋白在细胞-细胞接触处表达，但在HSC 2、HSC 3和HSC 4中，桥粒斑蛋白在细胞内扩散。OSCC可能与淋巴管结合，细胞表面暴露的桥粒斑蛋白在细胞上过表达。此外，具有p53突变体的细胞系和组织中的OSCC细胞也在细胞内过表达桥粒斑蛋白。桥粒斑蛋白的过度表达可能与p53突变有关。在人新生儿淋巴管内皮细胞（HNDLEC）的细胞生长试验中，发现没有血管内皮生长因子（VEGF）和胰岛素样生长因子（IGF），HNDLEC不能增殖。HNDLEC与HSC 2、HSC 3、HSC 4、HO 1 myu 1、HO 1 N1、Ca. 922、SAS、KB共培养后的增殖实验结果表明，HNDLEC与HSC 3、HO 1 myu 1、SAS共培养后，细胞活力维持时间较长。某些口腔鳞癌可能产生淋巴管生成所需的生长因子。