Amplification of telomeric DNA directly correlates with metastatic potential of human and murine cancers of various histological origin

Telomeres, repeated DNA sequences (T(2)AG(3))n that guard the ends of chrom osomes, serve as a checkpoint for cell-cycle progression and regulate cell senescence and apoptosis. Loss of the telomeric repeats promotes genomic in stability, which is the hallmark of most cancer cells. Whether this loss di ffers among tumor cells with malignant potential is unknown and was the goa l of this study. An all-human telomeric DNA probe was used to perform fluor escence in situ hybridization (FISH) and the telomeric signals in interphas e nuclei were quantitated using a computer software package. Southern blot analysis was carried out to measure terminal restriction fragment length (T RFL) in multiple cancer cell lines, including nonmetastatic and metastatic human breast, lung, prostate, colon, brain, and renal carcinomas, as well a s human and murine melanoma clones and somatic cell hybrids. The metastatic capability of all cell lines, clones and somatic cell hybrids was evaluate d subsequent to orthotopic implantation into nude mice. FISH preparations w ith telomeric DNA probes showed that the mean percent telomeric area in the metastatic nuclei was significantly greater than their nonmetastatic count erparts and Southern blotting in selected samples confirmed our findings. T hese data suggest that amplification of telomeres is directly correlated wi th invasive and metastatic potential of murine or human tumor cells.