Development and characterization of a model of liver metastasis using human colon cancer HCT-116 cells.
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.
Ishizu
Kazuhiro
K
Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
Sunose
Naohide
N
Yamazaki
Kanami
K
Tsuruo
Takashi
T
Sadahiro
Sotaro
S
Makuuchi
Hiroyasu
H
Yamori
Takao
T
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D024043:Collagen Type II / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005467:Floxuridine / Q000627:therapeutic use; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D007797:Laminin / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000473:pathology* / Q000517:prevention & control; D017239:Paclitaxel / Q000627:therapeutic use