Volume 4, Issue 2 (June 2002) 4, 123–129;
Mechanisms of metastasis suppression by introduction of human chromosome 10 into rat prostate cancer
M. Hamano, H. Kuramochi, N. Nihei, N. Kamiya, H. Suzuki, T. Igarashi, J.C. Barrett, T. Ichikawa, H. Ito
1.Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan 2.Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 3.Department of Molecular Oncology and Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan
Advance online publication 1 June 2002
Abstract |
Aim: The metastatic ability of a Dunning R-3327 rat prostate cancer subline (AT6.3) was suppressed by the introduction of human chromosome 10, when these hybrid cancer cells were injected subcutaneously into nude mice (Nihei et al., Genes Chromosomes Cancer 14:112-119, 1995). The present study was undertaken to clarify which step of metastasis was suppressed in the human chromosome 10-containing microcell hybrids (AT 6.3-10 clones). Methods: Gelatin zymography, an in vitro invasion assay using a Boyden chamber and an intravenous metastasis assay involving the injection of hybrid cells into nude mice were performed. Results: Gelatin zymography revealed that AT6.3-10 microcell hybrid clones expressed the 72 kD type IV collagenase (MMP-2) at an almost equal level as control microcell hybrid clones. Both the invasiveness as measured by the invasion assay and the number of lung metastases as measured by the intravenous metastasis assay of AT6.3-10 hybrid clones were significantly less than those of the AT6.3 parental clone. Conclusion: The human chromosome 10 suppresses both the local invasion and the metastatic process after entry into the blood circulation of rat prostate cancer. This decrease in local-invasive ability does not seem to require a decrease in MMP-2 activity.
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