Clinical utility of telomerase in cancer

Hiyama, Eiso; Hiyama, Keiko

doi:10.1038/sj.onc.1205070

Cited by 181 publications

(126 citation statements)

References 67 publications

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“…Since the detection of telomerase activity has generated considerable interest as a diagnostic tool, the observation of hTERT autoantibodies in the sera derived from cancer patients suggests that such autoantibodies constitute novel and specific tumor markers as a possible impact diagnostic tool (Hiyama and Hiyama, 2002). In this sense, these results strongly suggest that serum anti-hTERT auto-antibodies would become a possible novel early tumor marker in hepatocellular carcinoma.…”

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confidence: 80%

Identification of serum anti-human telomerase reverse transcriptase (hTERT) auto-antibodies during progression to hepatocellular carcinoma

et al. 2002

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confidence: 80%

Identification of serum anti-human telomerase reverse transcriptase (hTERT) auto-antibodies during progression to hepatocellular carcinoma

et al. 2002

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“…Telomerase is inactive in most normal somatic tissues except for germ and some stem cells, but has been found to be reactivated in approximately 85% of human malignancies [17,18] . Telomerase activity can be detected in trace amount of tissues, such as that collected in fine-needle aspiration cytology or even in the body fluid of cancer patients [19] . Recently, telomerase expression also was found in peritoneal fluid of patients with gastric cancer [20][21][22] .…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of telomerase activity in peritoneal lavage fluid from patients with gastric cancer and its relationship with cellular proliferation

Wu²,

Guo³

et al. 2007

WJG

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AIM:To evaluate the efficacy of telomerase activity assay and peritoneal lavage cytology (PLC) examination in peritoneal lavage fluid for the prediction of peritoneal metastasis in gastric cancer patients, and to explore the relationship between telomerase activity and proliferating cell nuclear antigen expression. METHODS:Telomeric repeated amplification protocol (TRAP)-enzyme-linked immunosorbent assay (ELISA) was performed to measure the telomerase activity in 60 patients with gastric cancer and 50 with peptic ulcer. PLC analysis of the 60 patients with gastric cancer was used for comparison. The proliferating cell nuclear antigen (PCNA) in gastric carcinoma was immunohistochemically examined. RESULTS:The telomerase activity and PLC positive rate in peritoneal lavage fluid from patients with gastric cancer was 41.7% (25/60), and 25.0% (15/60), respectively. The positive rate of telomerase activity was significantly higher than that of PLC in the group of pT4 (15/16 vs 9/16, P < 0.05), P1-3 (13/13 vs 9/13, P < 0.05) and diffuse type (22/42 vs 13/42, P < 0.05).The patients with positive telomerase activity, peritoneal metastasis, and serosal invasion had significantly higher levels of average PCNA proliferation index (PI), (55.00 ± 6.59 vs 27.43 ± 7.72, 57.26 ± 10.18 vs 29.15 ± 8.31, and 49.82 ± 6.74 vs 24.65 ± 7.33, respectively, P < 0.05). CONCLUSION:The TRAP assay for telomerase activity is a useful adjunct for cytologic method in the diagnosis of peritoneal micrometastasis and well related to higher proliferating activity of gastric cancer. The results of this study also suggest a promising future therapeutic strategy for treating peritoneal dissemination based on telomerase inhibition.

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“…The most extensively characterized function of telomerase is to maintain the telomeric repeats capping the ends of eukaryotic chromosomes and thereby preserve their integrity by preventing end-to-end fusions (1)(2)(3)(4). Whereas normal somatic cells have diminished telomerase activity, Ͼ90% of human cancers overexpress telomerase (5,6). The well established roles for telomerase in tumor initiation and cellular immortalization (7,8) have led to the identification of telomerase as a potentially important molecular target in cancer therapeutics (9)(10)(11).…”

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confidence: 99%

Genes and pathways downstream of telomerase in melanoma metastasis

Bagheri

Nosrati

Li³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

124

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Recent studies have demonstrated a role for telomerase in driving tumor progression, but its mechanism of action remains unclear. Here we show that stable, ribozyme-mediated suppression of mouse telomerase RNA reduced telomerase RNA expression, telomerase activity, and telomere length, which significantly reduced tumor invasion and metastatic potential. Our studies reveal that previously unidentified effects of telomerase may mediate its tumor-promoting effects. First, reducing telomerase activity induced a more dendritic morphology, accompanied by increased melanin content and increased expression of tyrosinase, a key enzyme in melanin biosynthesis. Second, gene expression profiling revealed that telomerase targeting down-regulated expression of several glycolytic pathway genes, with a corresponding decrease in glucose consumption and lactate production. Thus, telomerase activity controls the glycolytic pathway, potentially altering the energy state of tumor cells and thereby modulating tyrosinase activity and melanin production. These studies have important implications for understanding the mechanisms by which telomerase promotes tumor invasion and metastasis.differentiation ͉ glycolysis T elomerase is a ribonucleoprotein complex composed of core protein (telomerase reverse transcriptase) and RNA (telomerase RNA or TER) moieties. The most extensively characterized function of telomerase is to maintain the telomeric repeats capping the ends of eukaryotic chromosomes and thereby preserve their integrity by preventing end-to-end fusions (1-4). Whereas normal somatic cells have diminished telomerase activity, Ͼ90% of human cancers overexpress telomerase (5, 6). The well established roles for telomerase in tumor initiation and cellular immortalization (7,8) have led to the identification of telomerase as a potentially important molecular target in cancer therapeutics (9-11). To date, multiple studies have examined the utility of targeting telomerase to inhibit tumor cell proliferation (12-16).Although the importance of telomerase for tumor cell proliferation is well documented, its impact on tumor invasion and metastasis has been studied less. In our recent study, we used a systemic injection model of an effective anti-telomerase ribozyme to reveal that inhibiting telomerase activity in tumorbearing mice significantly reduces metastatic progression (16). Here, we examine the direct role played by telomerase in the metastatic potential of murine melanoma and characterize cellular pathways altered by telomerase suppression in tumor cells. We show that stable, ribozyme-mediated suppression of TER levels in melanoma cells results in a more dendritic phenotype, accompanied by increased tyrosinase expression and pigment production. Furthermore, we show that TER suppression results in down-regulation of glycolytic pathway genes and significantly reduces glucose metabolism, providing a mechanistic basis for the reduced metastatic capacity and increased pigment production observed. ResultsTo directly examine the role of te...

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Clinical utility of telomerase in cancer

Cited by 181 publications

References 67 publications

Identification of serum anti-human telomerase reverse transcriptase (hTERT) auto-antibodies during progression to hepatocellular carcinoma

Identification of serum anti-human telomerase reverse transcriptase (hTERT) auto-antibodies during progression to hepatocellular carcinoma

Clinical significance of telomerase activity in peritoneal lavage fluid from patients with gastric cancer and its relationship with cellular proliferation

Genes and pathways downstream of telomerase in melanoma metastasis

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