British Journal of Cancer (2001) 84, 631–635. doi:10.1054/bjoc.2000.1662 www.bjcancer.com
Published online 27 February 2001
Detection of circulating carcinoma cells by telomerase activity
L R Gauthier1, C Granotier1, J-C Soria2, S Faivre2, V Boige2, E Raymond2 and F D Boussin1
- 1Laboratoire de RadioPathologie, DRR/DSV CEA BP6, Fontenay-aux-Roses, 92265, France
- 2Département de Médecine, Institut Gustave Roussy, Villejuif, 94805, France
Received 10 August 2000; Revised 20 November 2000; Accepted 29 November 2000.
Top of pageAbstract
Telomerase has been shown to be a marker of epithelial cancer cells. We developed a method that allows the detection of circulating carcinoma cells in the blood of cancer patients. Circulating epithelial cells are harvested from peripheral blood mononuclear cells by immunomagnetic separation using BerEP4-coated beads. A telomeric repeat amplification protocol (TRAP)-ELISA is then used to measure telomerase in harvested epithelial cells. This method is specific and sensitive as demonstrated by experiments using BerEP4-positive and negative cell lines. Whereas we never found telomerase activity in harvested epithelial cells (HEC) samples from 30/30 healthy donors, we have detected telomerase activity in HEC from 11/15 (73%) patients with stage IIIB or IV non-small cell lung cancer (NSCLC) patients and from 8/11 (72%) stage C or D (Dukes classification) colon cancer patients. This non-invasive method could be of great value as a diagnostic or prognostic marker, or for monitoring cancer progression. © 2001 Cancer Research Campaign
Keywords:
circulating tumour cells, carcinoma, telomerase
Top of pageReferences
- Albanell J, Lonardo F, Rusch V, Engelhardt M, Langenfeld J, Han W, Klimstra D, Venkatraman E, Moore MA and Dmitrovsky E (1997) High telomerase activity in primary lung cancers: association with increased cell proliferation rates and advanced pathologic stage. J Natl Cancer Inst 89: 1609–1615 | Article | PubMed | ChemPort |
- Bostick PJ, Chatterjee S, Chi DD, Huynh KT, Giuliano AE, Cote R and Hoon DS (1998) Limitations of specific reverse-transcriptase polymerase chain reaction markers in the detection of metastases in the lymph nodes and blood of breast cancer patients. J Clin Oncol 16: 2632–2640 | PubMed | ISI | ChemPort |
- Broccoli D, Young JW and de Lange T (1995) Telomerase activity in normal and malignant hematopoietic cells. Proc Natl Acad Sci USA 92: 9082–9086 | Article | PubMed | ChemPort |
- Diel IJ, Kaufmann M, Costa SD, Holle R, von Minckwitz G, Solomayer EF, Kaul S and Bastert G (1996) Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status [see comments]. J Natl Cancer Inst 88: 1652–1658 | Article | PubMed | ChemPort |
- Engelhardt M, Drullinsky P, Guillem J and Moore MA (1997) Telomerase and telomere length in the development and progression of premalignant lesions to colorectal cancer. Clin Cancer Res 3: 1931–1941 | PubMed | ISI | ChemPort |
- Ghossein RA, Coit D, Brennan M, Zhang ZF, Wang Y, Bhattacharya S, Houghton A and Rosai J (1998) Prognostic significance of peripheral blood and bone marrow tyrosinase messenger RNA in malignant melanoma. Clin Cancer Res 4: 419–428 | PubMed | ISI | ChemPort |
- Hardingham JE, Kotasek D, Sage RE, Eaton MC, Pascoe VH and Dobrovic A (1995) Detection of circulating tumor cells in colorectal cancer by immunobead-PCR is a sensitive prognostic marker for relapse of disease. Mol Med 1: 789–794
- Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, Piatyszek MA, Shay JW, Ishioka S and Yamakido M (1995) Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol 155: 3711–3715 | PubMed | ISI | ChemPort |
- Jung R, Petersen K, Kruger W, Wolf M, Wagener C, Zander A and Neumaier M (1999) Detection of micrometastasis by cytokeratin 20 RT-PCR is limited due to stable background transcription in granulocytes. Br J Cancer 81: 870–873 | Article | PubMed | ISI | ChemPort |
- Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL and Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer [see comments]. Science 266: 2011–2015 | Article | PubMed | ISI | ChemPort |
- Kolquist KA, Ellisen LW, Counter CM, Meyerson M, Tan LK, Weinberg RA, Haber DA and Gerald WL (1998) Expression of TERT in early premalignant lesions and a subset of cells in normal tissues [see comments]. Nat Genet 19: 182–186 | Article | PubMed | ISI | ChemPort |
- Latza U, Niedobitek G, Schwarting R, Nekarda H and Stein H (1990) Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelial. J Clin Pathol 43: 213–219 | Article | PubMed | ISI | ChemPort |
- Marchetti A, Bertacca G, Buttitta F, Chella A, Quattrocolo G, Angeletti CA and Bevilacqua G (1999) Telomerase activity as a prognostic indicator in stage I non-small cell lung cancer. Clin Cancer Res 5: 2077–2081 | PubMed | ISI | ChemPort |
- Pantel K, Izbicki J, Passlick B, Angstwurm M, Haussinger K, Thetter O and Riethmuller G (1996) Frequency and prognostic significance of isolated tumour cells in bone marrow of patients with non-small-cell lung cancer without overt metastases. Lancet 347: 649–653 | Article | PubMed | ISI | ChemPort |
- Soria JC, Gauthier LR, Raymond E, Granotier C, Morat L, Armand JP, Boussin FD and Sabatier L (1999) Molecular detection of telomerase-positive circulating epithelial cells in metastatic breast cancer patients. Clin Cancer Res 5: 971–975 | PubMed | ISI | ChemPort |
- Taga S, Osaki T, Ohgami A, Imoto H and Yasumoto K (1999) Prognostic impact of telomerase activity in non-small cell lung cancers. Ann Surg 230: 715–720 | Article | PubMed | ISI | ChemPort |
- Tahara H, Kuniyasu H, Yokozaki H, Yasui W, Shay JW, Ide T and Tahara E (1995) Telomerase activity in preneoplastic and neoplastic gastric and colorectal lesions. Clin Cancer Res 1: 1245–1251 | PubMed | ISI | ChemPort |
- Yoshida R, Kiyozuka Y, Ichiyoshi H, Senzaki H, Takada H, Hioki K and Tsubura A (1999) Change in telomerase activity during human colorectal carcinogenesis. Anticancer Res 19: 2167–2172 | PubMed |