Ishizu Kazuhiro, Sunose Naohide, Yamazaki Kanami, Tsuruo Takashi, Sadahiro Sotaro, Makuuchi Hiroyasu, Yamori Takao
Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
Biol Pharm Bull. 2007 Sep;30(9):1779-83. doi: 10.1248/bpb.30.1779.
In order to develop a model of liver metastasis of human gastrointestinal cancer cells, we examined the potential of 10 human colon and stomach cancer cell lines (HT-29, WiDr, HCT-116, HCT-15, HCC-2998, MKN7, MKN28, MKN45, MKN74 and St-4) to form liver metastases in nude mice. Among the cell lines, HCT-116 cells consistently formed gross liver metastases when injected into the spleens of nude mice. In contrast, other human colon and stomach cancer cells produced little or no liver metastasis. In order to analyze the high metastatic potential of HCT-116 cells, the adhesion potential was compared between HCT-116 cells and the other colon cancer cell lines. HCT-116 cells showed more efficient adhesion to fibronectin (FN) than other cells. Furthermore, FN enhanced haptotaxis of HCT-116 cells, but not of other colon cancer cells. The high adhesion potential to FN and enhanced haptotaxis may contribute, at least in part, to the high metastatic potential of HCT-116. To assess the value of this newly developed model of liver metastasis, we compared the ability of four anticancer drugs (fluorouracil, doxifluridine, paclitaxel and irinotecan) to inhibit the formation of liver metastases. Paclitaxel and irinotecan showed strong inhibition of liver metastasis but fluorouracil and doxifluridine showed only slight inhibition. Therefore, this model of metastasis may be useful for screening anti-liver metastatic reagents. These results indicate that the HCT-116 liver-metastasis model should be useful for analyzing the molecular mechanism of liver metastasis and for evaluating new anti-liver metastatic drugs.
为了建立人胃肠道癌细胞肝转移模型，我们检测了10种人结肠和胃癌细胞系（HT-29、WiDr、HCT-116、HCT-15、HCC-2998、MKN7、MKN28、MKN45、MKN74和St-4）在裸鼠体内形成肝转移的潜力。在这些细胞系中，将HCT-116细胞注射到裸鼠脾脏后，始终能形成明显的肝转移灶。相比之下，其他的人结肠和胃癌细胞很少产生或不产生肝转移。为了分析HCT-116细胞的高转移潜力，比较了HCT-116细胞与其他结肠癌细胞系之间的黏附潜力。HCT-116细胞比其他细胞对纤连蛋白（FN）表现出更有效的黏附。此外，FN增强了HCT-116细胞的趋触性，但对其他结肠癌细胞没有增强作用。对FN的高黏附潜力和增强的趋触性可能至少部分地促成了HCT-116的高转移潜力。为了评估这个新建立的肝转移模型的价值，我们比较了四种抗癌药物（氟尿嘧啶、去氧氟尿苷、紫杉醇和伊立替康）抑制肝转移形成的能力。紫杉醇和伊立替康对肝转移有强烈的抑制作用，但氟尿嘧啶和去氧氟尿苷仅表现出轻微的抑制作用。因此，这个转移模型可能有助于筛选抗肝转移试剂。这些结果表明，HCT-116肝转移模型对于分析肝转移的分子机制和评估新的抗肝转移药物应该是有用的。
