Development and Characterization of a Model of Liver Metastasis Using Human Colon Cancer HCT-116 Cells

Abstract

The control of cancer metastasis is one of the most important strategies for cancer therapy from the current viewpoint of considerable limitations of surgical cancer resection. During the process of metastasis, metastasizing tumor cells interact with various host cells (platelets, lymphocytes and endothelial cells), extracellular matrix and basement membranes, leading to the development of metastases. [1][2][3][4][5][6][7][8][9] Experimental models are essential for the analysis of the mechanisms of cancer metastasis and a number of animal models have been developed. Although these have been extremely useful for the elucidation of the mechanism of cancer metastasis, the number of metastatic models based on human cancer cell lines is limited. 6,7,[10][11][12] From a clinical point of view, the liver is the most common target organ for metastasis of cancers of the digestive system, especially hematogenous metastasis of colon cancer, and the prognosis for cases with liver metastasis is extremely poor. Millikan et al. 13) reported that, considering the metastasis of colon cancer, up to 25% of patients have synchronous hepatic metastasis and 50% develop metachronous metastasis. Welch and Donaldson 14) reported that the liver is the most frequent target organ of hematogenous metastasis from colon cancer and 40-70% of the deaths from colon cancer involved liver metastasis. Russell et al. 15) reported that the first relapse site of 80% of colon cancer was the liver and 32% of the recurrence was only in the liver. Furthermore, liver metastasis often was observed after radical surgery.16) Therefore, analyzing the mechanism of liver metastasis and the improving its treatment are the most important considerations for improving the survival rate in colon cancer.To this end, suitable experimental models are needed for liver metastasis of human gastro-intestinal cancer. There are some models, for example, one of which was developed by Morikawa et al. 17) However, their number and variety are quite limited. In this study, to develop a liver-metastasis model of gastro-intestinal cancer, we screened human gastric cancer and colon cancer cell lines for their liver-metastatic potential, and found that one of the colon adenocarcinoma cell line, HCT-116, was suitable for developing such a model. The suitability of the HCT-116 liver metastasis model for the evaluation of anti metastatic reagents was confirmed using paclitaxel and irinotecan as model drugs. MATERIALS AND METHODSMice Animal care and treatment was performed in accordance with the guidelines of the animal use and care committee of Japanese Foundation for Cancer Research, and conformed to the NIH 'Guide for the Care and Use of Laboratory Animals'. All procedures were approved by the above committee. Seven-to-nine week old female nude mice (BALB/C nu/nu) were purchased from Charles River Japan, Inc. The mice were maintained in the laboratory for animal experimentation in a Specific Pathogen Free environment.Cell Lines The human colon and stomach cancer cell lines us...

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