Reversibility of DNA Ploidy Changes Observed in Pulmonary metastasis in the Murine Osteosarcoma after Orthotopic Implantation

Kim, Ju O

Abstract

The difference in DNA ploidy pattern between primary and metastatic tumor remains an interesting question. We examined whether the observed change of tumor ploidy is permanent or whether it is reversible after reinoculation of the metastatic foci to an orthotopic site of another mouse. We isolated 14 metastatic pulmonary nodules from 8 mice with MGH-OGS murine osteosarcoma of thigh, and inoculated these nodules into the thighs of twenty nine C3H/Sed mice. In addition, we performed the cytoflowmetric examination of the primary tumor, the inoculated metastatic pulmonary nodules, and the regrown tumor after orthotopic inoculation. In the primary thigh tumor of FS MGH-OGS mice, the ploidy pattern was primarily aneuploid(Average values were % Diploid Cells: 23% and the mean DNA Index: 1.39). Examination of the pulmonary nodule revealed a significant increase in the diploid cell population(Mean: 54%) in 79% of nodules and a significant decrease in the mean DNA Index(Mean: 1.24) in 50% of the nodules. The tumors regrown after orthotopic implantation of metastatic pulmonary nodules however showed the same ploidy pattern and regrown parameters as was seen in the primary tumor, regardless of the ploidy pattern of the implanted metastatic nodules. This data support the concept that the lesion that goes to the lung may have hyperpercentage of surviving diploid cells(rather than aneuploid), but once reimplanted into the "native" site became primarily aneuploid again.