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J Cancer Res Clin Oncol. 2004 Aug;130(8):460-8. Epub 2004 May 14.

Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristics.

Author information

1
Liver Cancer Institute & Zhong Shan Hospital of Fudan University, 136 Yi Xue Yuan Road, 200032 Shanghai, China.

Abstract

PURPOSE:

To establish a "stepwise metastatic human hepatocellular carcinoma (HCC) cell model system" for in-depth study of the underlying mechanisms of HCC metastasis.

METHODS:

Using MHCC97- a metastatic human hepatocellular carcinoma (HCC) cell line reported in 1999-as the parent cells, we subsequently established three cell lines (MHCC97-L, HMCC97-H, and HCCLM3) with increasing spontaneous metastatic potential. Now, the fourth cell line with unique multiple metastatic characteristics has been established by six rounds of in vivo selection.

RESULTS:

This cell line, designated as HCCLM6, is a polygonal epithelial cell with hypotriploid karyotype, the modal chromosomes are 55-58, and marker chromosomal abnormalities include i(1) (q10), i(8)(q10), der (4) t(4;8)(q31;q22), i(X)(q10). The cell population doubling time was 32 h. Fluorescent PCR showed HBV DNA integration in the cellular genome. Thirty-five days after HCCLM6 was injected subcutaneously into BALB/c nude mice, prominent lung metastases occurred in 100% of the recipient animals. When tumor tissue was orthotopically implanted into the liver of nude mouse, widespread loco-regional and pulmonary metastases occurred. Inoculation of this cell into the footpad of nude mice also produced 75% regional lymph node metastasis. Compared with MHCC97-L which was not metastastatic via subcutaneous or footpad inoculation and 40% metastatic via orthotopic inoculation, HCCLM6 had increased expression of matrix metalloproteinase (MMP-2 and MMP-9) and cytokeratin 19 (CK19), and decreased expression of Rb2/p130. The establishment of this new cell line has completed our stepwise metastatic HCC cell mode system, which was characterized by a similar genetic background but with significant differences in spontaneous metastasis behavior.

CONCLUSIONS:

The study supports the theory that cancer metastasis is a highly selective dynamic process and the cell model system could be a useful platform for the study of HCC metastasis.

PMID:
15146329
DOI:
10.1007/s00432-004-0564-9
[Indexed for MEDLINE]

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