N. Sato et al., Telomerase activity of cultured human pancreatic carcinoma cell lines correlates with their potential for migration and invasion, CANCER, 91(3), 2001, pp. 496-504
BACKGROUND, Despite the recent clinical finding that high telomerase activi
ty is an unfavorable prognostic marker for various human malignant tumors,
there has been no experimental evidence supporting the link between telomer
ase and tumor aggressiveness. In the current investigation, the authors exa
mined the relation between telomerase activity and potential for biologic a
ggressiveness in human pancreatic carcinoma cells.
METHODS. Telomerase activity was measured in a poorly metastatic cell line
HPC-3 and its highly metastatic variant HPC-3H4, as well as in many pancrea
tic carcinoma cell lines. Aggressive behavior of cancer cells was assessed
by in vitro migration and invasion assay.
RESULTS. Compared with parental HPC-3, HPC-3H4 displayed higher telomerase
activity, which was associated with a scattered phenotype and enhanced migr
ation activity. Furthermore, the authors found that relative telomerase lev
els correlated well with both motility (P = 0.0041) and invasion (P = 0.011
4) in 13 pancreatic carcinoma cell lines. There was, however, no significan
t association between telomerase activity and cell proliferation. When telo
merase activity of KP-1N cells was inhibited by transfection with antisense
oligonucleotides, their motility and invasion rates were significantly dec
reased.
CONCLUSIONS. The authors concluded that the magnitude of telomerase activat
ion may reflect the potential for aggressive behavior within cancer cells.
These findings support the clinical utility of telomerase activity as a pro
gnostic indicator. Their results also suggest a therapeutic potential for t
elomerase inhibitors to prevent tumor invasion and possibly metastasis. (C)
2001 American Cancer Society.