Telomerase activity of cultured human pancreatic carcinoma cell lines correlates with their potential for migration and invasion.
BACKGROUND
Despite the recent clinical finding that high telomerase activity is an unfavorable prognostic marker for various human malignant tumors, there has been no experimental evidence supporting the link between telomerase and tumor aggressiveness. In the current investigation, the authors examined the relation between telomerase activity and potential for biologic aggressiveness 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 pancreatic 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 migration activity. Furthermore, the authors found that relative telomerase levels correlated well with both motility (P = 0.0041) and invasion (P = 0.0114) in 13 pancreatic carcinoma cell lines. There was, however, no significant association between telomerase activity and cell proliferation. When telomerase activity of KP-1N cells was inhibited by transfection with antisense oligonucleotides, their motility and invasion rates were significantly decreased.


CONCLUSIONS
The authors concluded that the magnitude of telomerase activation may reflect the potential for aggressive behavior within cancer cells. These findings support the clinical utility of telomerase activity as a prognostic indicator. Their results also suggest a therapeutic potential for telomerase inhibitors to prevent tumor invasion and possibly metastasis.
Sato
N
N
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Maehara
N
N
Mizumoto
K
K
Nagai
E
E
Yasoshima
T
T
Hirata
K
K
Tanaka
M
M
D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D009361:Neoplasm Invasiveness; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D016376:Oligonucleotides, Antisense; D019098:Telomerase