Establishment of highly metastatic models for human gastric cancer in nude mice and analysis of factors that regulate the metastatic modes.

目前调控人胃癌各种转移模型的机制尚不清楚，有必要建立适合于血行、淋巴和腹膜转移研究的体内实验模型。为此，我们利用裸鼠体内分步筛选的方法建立了肝转移能力较强的AZH5G细胞系、淋巴结转移能力较强的AZL5G细胞系和腹膜转移能力较低的人胃癌AZ521细胞系AZ-P7a细胞系，与亲代AZ521细胞相比，三株高转移能力细胞株的运动能力和生长活性均明显增强，表明无论转移方式如何，AZL5G和AZ-P7a都参与了转移潜能的增强。在细胞表面黏附分子方面，AZL5G提示α-2、α-3、α-5、α-6和αυβ-3整合素表达上调，而α-3、α-5整合素表达增加，α-6整合素表达降低。CD44家族、免疫球蛋白超家族、钙粘附素等黏附分子在所有细胞系中均不表达。AZL5G细胞对4型胶原和纤维连接蛋白的黏附活性明显高于AZ521细胞，而AZ-P7a细胞对这些细胞外基质蛋白的黏附活性明显低于AZ521细胞。这些发现表明，整合素的表达和对ECMPs的粘附性的变化可能参与了人胃癌转移模式的调节。

The actual mechanisms that regulate various models of metastasis by human gastric cancer are still unclear, and there is a need to establish in vivo experimental models suitable for the investigation of hematogenous, lymphogenous and peritoneal metastases. For the purpose, we established highly liver-metastasizing line, designated AZH5G, lymph node-metastasizing line, AZL5G, and peritoneum-metastasizing line, AZ-P7a, which were derived from the same human gastric cancer cell line, AZ521, with low metastatic potential using in vivo stepwise selection in nude mice.All of three high-metastatic lines showed clearly increased motility and growth activity compared with the parental AZ521 cells, indicating that those properties are involved in the enhancement of metastatic potential regardless of metastatic modes. Concerning cell surface adhesion molecules, AZL5G expressed suggestive up-regulation of α2, α3, α5, α6 and αυβ3 integrins while AZH5G showed increased expression of α3 and α5 integrins and decreased expression of α6 integrin. The other adhesion molecules such as CD44 family, immunoglobulin superfamily or cadherin were not expressed in any cell lines. The adhesive activity of AZL5G cells to type-4 collagen and fibronectin was clearly increased than that of AZ521 cells, while contrast, the adhesive activity of AZ-P7a cells to these extracellular matrix proteins (ECMPs) was significantly decreased than that of AZ521 cells. These findings suggest that changes both in the expression of integrins and in adhesiveness to ECMPs may be involved in the regulation of metastatic mode in human gastric carcinomas.