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ESTABLISHMENT OF ANTI-LYMPHANGIOGENETIC THERAPY BY CANCER SPECIFIC s-VEGFR-3.

癌症特异性 s-VEGFR-3 抗淋巴管发生疗法的建立。

基本信息

批准号：
16592020
负责人：
HATORI Masashi
金额：
$ 2.3万
依托单位：
SHOWA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16592020/
关键词：
VFGF VEGFR-3 LYMPHANGIOGENESIS HGF c-Met HIF SQUAMOUS CELL CARCINOMA MMP HIF-1α

项目摘要

Expression of VEGF family in OSCC cell lines.To examine the expression profile of VEGF family on squamous cell carcinoma cell lines NA and HSC-4, we performed RT-PCR analysis. As results, both cells expressed VEGF-C and VEGF-D. The expression of VEGFR was not detected in both cells.Involvement of HGF-Met system in the invasiveness of OSCC cells.It is well known that the expression of VEGF is highly regulated by c-Met, a counter part of hepatocyto growth factor (HGF). Thus, we examined the expressions of c-Met and HGF by RT-PCR in both OSCC cells. Although HGF was not expressed in OSCC cells, c-Met was highly expressed in both cells.The cancer cells survive in the situation of low oxygen called HYPOXIA in tumor mass. The cells under hypoxia express HIF, a nuclear factor and acquire the survival potential. HIF exist in upstream of c-Met,MMPs,VEGF and influence the invasiveness of cancer cells. Therefore, we performed RT-PCR for HIF on OSCC cells in hypoxia chamber. Both cells expressed HIF-1 in hypoxia and c-Met is also induced. Interestingly, invasion assay in hypoxia chamber revealed highly invasiveness of OSCC cells. To examine the mechanism of this up-regulation of invasiveness, we performed RT-PCR, western blotting and ELISA for MMP-2, a major matrix metalloproteinase for resolution of basement membrane in human. As results, the cells cultured in hypoxia chamber expressed high concentration of MMP-2 in the culture supernatant.

VEGF家族在OSCC细胞系中的表达。为了检测VEGF家族在鳞状细胞癌细胞株NA和HSC-4上的表达谱，我们采用RT-PCR分析。结果，两种细胞均表达VEGF-C和VEGF-D。两种细胞均未检测到VEGFR的表达。HGF-Met系统参与OSCC细胞的侵袭。众所周知，VEGF的表达受c-Met的高度调控，c-Met是肝细胞生长因子（HGF）的对应物。因此，我们通过RT-PCR检测了c-Met和HGF在两种OSCC细胞中的表达。虽然HGF在OSCC细胞中不表达，但c-Met在两种细胞中均有高表达。肿瘤细胞在低氧的情况下存活，称为缺氧。缺氧条件下的细胞表达核因子HIF，获得生存潜能。HIF存在于c-Met、MMPs、VEGF的上游，影响癌细胞的侵袭性。因此，我们在缺氧室对OSCC细胞进行了HIF的RT-PCR检测。两种细胞在缺氧和c-Met诱导下均表达HIF-1。有趣的是，缺氧室侵袭实验显示OSCC细胞具有高度侵袭性。为了研究这种侵袭性上调的机制，我们对人基底膜溶解的主要基质金属蛋白酶MMP-2进行了RT-PCR、western blotting和ELISA检测。结果表明，缺氧室培养的细胞在培养上清液中表达高浓度的MMP-2。