Tumor cells fail to trans-induce telomerase in human umbilical vein endothelial cell cultures

The shortening of the telomeres that occurs in most somatic cells and untransformed cell cultures is considered a hallmark of cellular senescence. Re-activation of telomerase, which is usually present in immortal cells, avoids telomere shortening and considerably extends the culture life span. Normal human endothelial cells are characterized by an accelerated rate of telomere shortening and reach replicative senescence after a limited number of cell divisions. It has recently been reported that human telomerase reverse transcriptase expression may be strongly up-regulated in human endothelial cells cocultivated with tumor cells. Due to the important implications of this finding on tumor progression, we have extensively analyzed for the presence of telomerase in primary human endothelial cells either cocultivated with tumor cells or grown with tumor-conditioned medium. We found modest, but readily detectable, amounts of telomerase in all human endothelial cell cultures analyzed that disappeared as the cultures approached senescence. Quantitative reverse transcription-PCR also showed a direct correlation between human telomerase reverse transcriptase expression and the proliferative index of the cultures. Nevertheless, we did not find any evidence of induction of telomerase activity by tumor cells in any of the tested conditions. All data indicate that telomerase in human endothelial cells follows an activation program that is strictly associated to the culture growth rate.