人肺上皮细胞、成纤维细胞、肺癌细胞间的异源间隙连接通讯

Selective heterologous communication among human lung epithelial cells, fibroblasts, and lung cancer PG cells

目的:探讨人肺成纤维细胞、上皮细胞间以及与人肺癌细胞的细胞间隙连接通讯(gapjunctionalintercel lularcommunication, GJIC)特性,以进一步了解GJIC在人肺癌发生、发展中的作用。方法:利用预标记荧光染料传输技术研究了人胚肺上皮类型细胞(HLEC)与人肺成纤维细胞HLF、肺癌PG细胞及其Cx43转染子PG/C4间的异源通讯,Cx43免疫荧光染色和Northern杂交分别检测Cx43蛋白和mRNA的表达。结果:尽管这些细胞除PG外都表达Cx43和具有强的同源通讯功能,但人肺上皮细胞HLEC与成纤维细胞间不能建立GJIC,上皮来源的人肺癌PG细胞与正常上皮细胞HLEC通讯功能缺陷; 具有强的同源通讯功能的Cx43转染子PG/C4并未建立与上皮细胞间的通讯功能。结论:人肺不同类型细胞间的GJIC存在选择性,细胞癌变后丧失了与其来源一致的上皮细胞间的通讯, Cx43基因表达并不足以建立二种细胞间的GJIC。

Objective: To further understand the roles of gap junctional intercellular communication in carcinogenesis and progression of human lung cancer. Methods: The heterologous communication was characterized among human lung epithelial cells HLEC, human lung fibroblasts HLF, human lung giant carcinoma PG cells and its Cx43 transfectants PG/C4 by using a preloading assay. Cx43 immunofluorescent staining and Northern blot were performed to examine Cx43 gene expression. Results: Although both human lung firoblasts HLF and epithelial cells HLEC expressed Cx43 and had very strong homologous communication, HLEC cells were unable to communicate with HLF cells. The human lung carcinoma cell line PG was defective of both homologous communication, and heterologous communication with its epithelial origin HLEC. Transfection of Cx43 into PG cells, which rescued PG cells' homologous communication and enhanced heterologous communication with HLF cells, could restore heterologous coupling with HLEC cells. Conclusion: Selective heterologous communication exists among different kinds of human lung cells. when human lung carcinoma cells lost coupling with its epithelial origin, Cx43 gene expression is not enough to establish heterologous communication between them.