Ohno K, Hata F, Nishimori H, Yasoshima T, Yanai Y, Sogahata K, Ezoe E, Tanaka H, Kamiguchi K, Isomura H, Denno R, Sato N, Hirata K
Dept. of Surgery 1, Sapporo Medical University School of Medicine, Sapporo, Japan.
J Exp Clin Cancer Res. 2003 Dec;22(4):623-31.
To elucidate metastasis mechanisms, we established a Panc-1H5 subline with a highly liver metastatic cell line and a Panc-1P4a with a highly peritoneal metastatic cell line, which were sequentially selected from the parental pancreatic cancer cell line Panc-1. Using these three cell lines, we investigated several biological properties and mRNA levels of differentially-expressed genes involved in cancer metastasis with a cDNA macroarray. The tumorigenicity, motile activity, adhesive activity and cytokine production of metastatic sublines were higher than those of parental Panc-1 cells. Particularly, in Panc-1H5 cells, adhesive activity to the extracellular matrix and angiogenetic factors increased, whereas in Panc-1P4a cells, motile activity was extremely enhanced compared with Panc-1 cells. Histopathological findings for the three cell lines were the same. In cDNA macroarray analysis of Panc-1H5 cells, 11 genes were up-regulated and 20 genes were down-regulated compared with parental Panc-1 cells. In Panc-1P4a cells, 7 genes were up-regulated and 13 genes were down-regulated compared with parental Panc-1 cells. This study provides a demonstration of global gene expression analysis of pancreatic cancer cells with liver and peritoneal metastasis and these results provide new insight into the study of human pancreatic cancer metastasis.
为了阐明转移机制，我们从亲本胰腺癌细胞系Panc-1中依次筛选建立了具有高肝转移能力的Panc-1H5亚系和具有高腹膜转移能力的Panc-1P4a亚系。利用这三种细胞系，我们通过cDNA宏阵列研究了参与癌症转移的几种生物学特性和差异表达基因的mRNA水平。转移亚系的致瘤性、运动活性、黏附活性和细胞因子产生均高于亲本Panc-1细胞。特别是，在Panc-1H5细胞中，对细胞外基质和血管生成因子的黏附活性增加，而在Panc-1P4a细胞中，与Panc-1细胞相比运动活性极度增强。这三种细胞系的组织病理学结果相同。在对Panc-1H5细胞的cDNA宏阵列分析中，与亲本Panc-1细胞相比，有11个基因上调，20个基因下调。在Panc-1P4a细胞中，与亲本Panc-1细胞相比，有7个基因上调，13个基因下调。本研究展示了对具有肝转移和腹膜转移的胰腺癌细胞进行全基因组表达分析，这些结果为人类胰腺癌转移的研究提供了新的见解。
