An experimental model for in vivo distant metastasis of human xenografts subcutaneously transplanted in imuune-deficient mice

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In this study, we established an experimental model for in vivo distant metastasis of human xenografts in severe combined immune deficient (SCID) mice. We examined non-metastatic (NM23) gene expression levels in the total 50 of various kinds of human tumor xenograts. We isolated human lung cancer xenografts LC-11JCK and LC-17JCK.The LC-17JCK did not express NM23 gene transcripts, whereas the LC-11JCK showed remarkable expression of NM23 gene. The xenogarafts were subcutaneously transplanted into the SCID mice. The mice were autopsied after transplantation to detect distant metastases into the lung or liver. We also examined the expression levels of vascular endothelial growth factor.The human lung cancer xenograft LC-17JCK showed remarkable liver and lung metastases 3 months after transplantation. However, the LC-11JCK did not show any distant metastasis in the mice. We also examined the metastatic incidence of the LC-17 in the SCID/beig mice. The distant metastasis is significantly increased in the SCID/beige mice. The function of natural killer cells are additionally suppressed in the SCID/beige mice. The LC-17 xenografts also showed an increased level of VEGF gene transcripts.These results suggest the expression levels of NM-23 gene and VEGF gene may related to distant metastases of the human lung cancer xenografts in vivo. This experimental model using severe combined immune deficient mice are potent system for the research of cancer metastasis.