Differential evolution in chromosomal composition during multiple cycles of subcutaneous and intravenous metastasis

Abstract

It has been proven that multiple cycles of metastasis can improve the metastatic potential and homing specificity of a tumor cell population. In the present study, verification of genetic alterations during changes in metastatic behavior was done by analyzing the chromosome composition of a methylcholanthrene induced murine fibrosarcoma, 3AM during multiple cycles of subcutaneous (SC) and intravenous (IV) metastasis. After 10 cycles of SC metastasis, a cell type, 7B, with a small t(19;19)(A;A) metacentric marker chromosome was enriched from 4% in the original population to 90% in FIOR. However, when the tumor cells were injected IV rather than SC, no enrichment of the 7B cell type was observed. Instead, a cell type AX with a large t(14;19)(E5;A) acrocentric marker chromosome was enriched from 1% in the parental population to 76% in F1OIV after 10 cycles of IV metastasis. The polyploid dominant FIOIV was found to be extremely high in IV metastasis (411 foci/lung) but low in SC metastasis (48 foci/lung). The diploid dominant FIOR appears to be high in both SC (163 foci/lung) and IV (301 foci/lung) metastasis. The data obtained suggest that metastasis will lead to the selection of specific preexisting cell types, and the type of cell selected will depend on the route of metastasis. Furthermore, during metastasis, new cell types may also be produced de novo through chromosomal structural and numerical aberrations.