Is gap junction the defensive factor against development, progression, and metastasis of gastric cancer?

本课题旨在探讨缝隙连接在胃癌发生、发展和转移中的作用。首先，证实了在兔胎胃粘膜细胞的培养和分化过程中形成了缝隙连接。接着，检查间隙连接在胃癌细胞系中的表达，并且在胃癌细胞系的培养和增殖期间没有表达。为探讨胃癌向正常组织侵袭和发展的机制，本研究采用胃癌细胞与正常胃粘膜细胞共培养的方法，观察胃癌细胞与正常胃粘膜细胞之间缝隙连接的表达及细胞增殖的变化。细胞间存在缝隙连接，胃癌细胞增殖活性降低。当时，人们认为这个项目可以完成。因此，接下来，研究间隙连接的表达是如何调节的。此外，证实了在胃癌细胞的培养过程中，包括WNT 8B和WNT 10B的Wnt信号传导增加。Wnt信号通路与缝隙连接的表达之间似乎存在着相互作用。此外，FRAT2，Wnt信号的介质，增加与胃癌细胞的增殖平行。从这些数据看来，缝隙连接的表达可能受到Wnt信号的调节。

The role of gap junction in development ,progression and metastasis of gastric cancer was investigated in this project. First, gap junction formation was confirmed to be made during the culture and differentiation of gastric mucosal cells originated from rabbit fetus. Next, the expression of gap junction in the gastric cancer cell lines was examined and there was no expression during the culture and proliferation of the gastric cancer cell lines. To investigate the mechanism of progression and invasion of gastric cancer to the normal tissues, the expression of gap junction as well as proliferation was investigated using the coculture of normal gastric mucosal cells and gastric cancer cells. There was seen a gap junction between two cells and the proliferation activity of gastric cancer cells was decreased. At that time, it was considered that this project can be finished. Therefore, next, it was investigated how the expression of gap junction was regulated. Furthermore, it was confirmed that Wnt signaling including WNT8B and WNT10B was increased during the culture of gastric cancer cells. It seems that there is a reciprocal change between Wnt signaling and the expression of gap junction. Also, FRAT2, a mediator of Wnt signaling, was increased in parallel with proliferation of gastric cancer cells. From these data, it seems that the expression of gap junction might be regulated by Wnt signaling.