Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance

Journal of Cancer Research and Clinical Oncology - Tập 137 Số 8 - Trang 1151-1173 - 2011
Yun-Fan Sun1, Xin‐Rong Yang1, Jian Zhou1, Shuang‐Jian Qiu1, Jia Fan2, Yang Xu2
1Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, People’s Republic of China
2Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhong Shan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People’s Republic of China

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Aktas B, Tewes M et al (2009) Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res 11(4):R46

Alix-Panabieres C, Vendrell JP et al (2007) Detection and characterization of putative metastatic precursor cells in cancer patients. Clin Chem 53(3):537–539

Alix-Panabieres C, Vendrell JP et al (2009) Full-length cytokeratin-19 is released by human tumor cells: a potential role in metastatic progression of breast cancer. Breast Cancer Res 11(3):R39

Allard WJ, Matera J et al (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10(20):6897–6904

Andreopoulou E, Cristofanilli M (2010) Circulating tumor cells as prognostic marker in metastatic breast cancer. Expert Rev Anticancer Ther 10(2):171–177

Ashida S, Okuda H et al (2000) Detection of circulating cancer cells with von hippel-lindau gene mutation in peripheral blood of patients with renal cell carcinoma. Clin Cancer Res 6(10):3817–3822

Attard G, Swennenhuis JF et al (2009) Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer Res 69(7):2912–2918

Balic M, Dandachi N et al (2005) Comparison of two methods for enumerating circulating tumor cells in carcinoma patients. Cytometry B Clin Cytom 68(1):25–30

Barrallo-Gimeno A, Nieto MA (2005) The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development 132(14):3151–3161

Bartels CL, Tsongalis GJ (2009) MicroRNAs: novel biomarkers for human cancer. Clin Chem 55(4):623–631

Bertazza L, Mocellin S et al (2009) Survivin gene levels in the peripheral blood of patients with gastric cancer independently predict survival. J Transl Med 7:111

Bidard FC, Mathiot C et al (2010) Clinical value of circulating endothelial cells and circulating tumor cells in metastatic breast cancer patients treated first line with bevacizumab and chemotherapy. Ann Oncol 21(9):1765–1771

Bluemke K, Bilkenroth U et al (2009) Detection of circulating tumor cells in peripheral blood of patients with renal cell carcinoma correlates with prognosis. Cancer Epidemiol Biomarkers Prev 18(8):2190–2194

Blumke K, Bilkenroth U et al (2005) Detection of circulating tumor cells from renal carcinoma patients: experiences of a two-center study. Oncol Rep 14(4):895–899

Botteri E, Sandri MT et al (2010) Modeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer. Breast Cancer Res Treat 122(1):211–217

Busch R, Cesar D et al (2004) Isolation of peripheral blood CD4(+) T cells using RosetteSep and MACS for studies of DNA turnover by deuterium labeling. J Immunol Methods 286(1–2):97–109

Cao W, Yang W et al (2011) Using detection of survivin-expressing circulating tumor cells in peripheral blood to predict tumor recurrence following curative resection of gastric cancer. J Surg Oncol 103(2):110–115

Chen BT, Loberg RD et al (2005) Preliminary study of immunomagnetic quantification of circulating tumor cells in patients with advanced disease. Urology 65(3):616–621

Chen TF, Jiang GL et al (2007) CK19 mRNA expression measured by reverse-transcription polymerase chain reaction (RT-PCR) in the peripheral blood of patients with non-small cell lung cancer treated by chemo-radiation: an independent prognostic factor. Lung Cancer 56(1):105–114

Cheng GZ, Chan J et al (2007) Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel. Cancer Res 67(5):1979–1987

Christofori G (2006) New signals from the invasive front. Nature 441(7092):444–450

Cohen SJ, Punt CJ et al (2008) Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 26(19):3213–3221

Cohen SJ, Punt CJ et al (2009) Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer. Ann Oncol 20(7):1223–1229

Coumans FA, Doggen CJ et al (2010) All circulating EpCAM+CK+CD45− objects predict overall survival in castration-resistant prostate cancer. Ann Oncol 21(9):1851–1857

Cristofanilli M (2009) The biological information obtainable from circulating tumor cells. Breast 18(suppl 3):S38–S40

Cristofanilli M, Budd GT et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351(8):781–791

Cristofanilli M, Hayes DF et al (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23(7):1420–1430

Danila DC, Heller G et al (2007) Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin Cancer Res 13(23):7053–7058

Davis JW, Nakanishi H et al (2008) Circulating tumor cells in peripheral blood samples from patients with increased serum prostate specific antigen: initial results in early prostate cancer. J Urol 179(6):2187–2191; discussion 2191

de Bono JS, Scher HI et al (2008) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14(19):6302–6309

de Cremoux P, Extra JM et al (2000) Detection of MUC1-expressing mammary carcinoma cells in the peripheral blood of breast cancer patients by real-time polymerase chain reaction. Clin Cancer Res 6(8):3117–3122

Desmedt C, Ruiz-Garcia E et al (2008) Gene expression predictors in breast cancer: current status, limitations and perspectives. Eur J Cancer 44(18):2714–2720

Drake JM, Strohbehn G et al (2009) ZEB1 enhances transendothelial migration and represses the epithelial phenotype of prostate cancer cells. Mol Biol Cell 20(8):2207–2217

Dubois SG, Epling CL et al (2010) Flow cytometric detection of Ewing sarcoma cells in peripheral blood and bone marrow. Pediatr Blood Cancer 54(1):13–18

Fabisiewicz A, Kulik J et al (2004) Detection of circulating breast cancer cells in peripheral blood by a two-marker reverse transcriptase-polymerase chain reaction assay. Acta Biochim Pol 51(3):747–755

Fehm T, Sagalowsky A et al (2002) Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant. Clin Cancer Res 8(7):2073–2084

Fehm T, Hoffmann O et al (2009) Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells. Breast Cancer Res 11(4):R59

Findeisen P, Rockel M et al (2008) Systematic identification and validation of candidate genes for detection of circulating tumor cells in peripheral blood specimens of colorectal cancer patients. Int J Oncol 33(5):1001–1010

Fong SM, Lee MK et al (2009) Fluorescence-expressing viruses allow rapid identification and separation of rare tumor cells in spiked samples of human whole blood. Surgery 146(3):498–505

Gallagher DJ, Milowsky MI et al (2009) Detection of circulating tumor cells in patients with urothelial cancer. Ann Oncol 20(2):305–308

Garcia JA, Rosenberg JE et al (2007) Evaluation and significance of circulating epithelial cells in patients with hormone-refractory prostate cancer. BJU Int 99(3):519–524

Geiger TR, Peeper DS (2009) Metastasis mechanisms. Biochim Biophys Acta 1796(2):293–308

Gertler R, Rosenberg R et al (2003) Detection of circulating tumor cells in blood using an optimized density gradient centrifugation. Recent Results Cancer Res 162:149–155

Goeminne JC, Guillaume T et al (2000) Pitfalls in the detection of disseminated non-hematological tumor cells. Ann Oncol 11(7):785–792

Gonzalez-Roca E, Garcia-Albeniz X et al (2010) Accurate expression profiling of very small cell populations. PLoS One 5(12):e14418

Goodman OB Jr, Fink LM et al (2009) Circulating tumor cells in patients with castration-resistant prostate cancer baseline values and correlation with prognostic factors. Cancer Epidemiol Biomarkers Prev 18(6):1904–1913

Gradilone A, Raimondi C et al (2011) Circulating tumor cells lacking cytokeratin in breast cancer: the importance of being mesenchymal. J Cell Mol Med 15(5):1066–1070

Guzzo TJ, McNeil BK et al (2009) The presence of circulating tumor cells does not predict extravesical disease in bladder cancer patients prior to radical cystectomy. Urol Oncol [Epub ahead of print]

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

Hartkopf AD, Wagner P et al (2011) Changing levels of circulating tumor cells in monitoring chemotherapy response in patients with metastatic breast cancer. Anticancer Res 31(3):979–984

Hayes DF, Cristofanilli M et al (2006) Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res 12(14 Pt 1):4218–4224

Hayes GM, Busch R et al (2010) Isolation of malignant B cells from patients with chronic lymphocytic leukemia (CLL) for analysis of cell proliferation: validation of a simplified method suitable for multi-center clinical studies. Leuk Res 34(6):809–815

Hofman V, Ilie MI et al (2010) Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small cell lung carcinoma: comparison of the efficacy of the CellSearch Assay and the isolation by size of epithelial tumor cell method. Int J Cancer [Epub ahead of print]

Hofman V, Bonnetaud C et al (2011) Preoperative circulating tumor cell detection using the isolation by size of epithelial tumor cell method for patients with lung cancer is a new prognostic biomarker. Clin Cancer Res 17(4):827–835

Hou JM, Greystoke A et al (2009) Evaluation of circulating tumor cells and serological cell death biomarkers in small cell lung cancer patients undergoing chemotherapy. Am J Pathol 175(2):808–816

Hou JM, Krebs M et al (2011) Circulating tumor cells as a window on metastasis biology in lung cancer. Am J Pathol 178(3):989–996

Howard EW, Leung SC et al (2008) Decreased adhesiveness, resistance to anoikis and suppression of GRP94 are integral to the survival of circulating tumor cells in prostate cancer. Clin Exp Metastasis 25(5):497–508

Hsieh HB, Marrinucci D et al (2006) High speed detection of circulating tumor cells. Biosens Bioelectron 21(10):1893–1899

Hu Y, Fan L et al (2010) Detection of circulating tumor cells in breast cancer patients utilizing multiparameter flow cytometry and assessment of the prognosis of patients in different CTCs levels. Cytometry A 77(3):213–219

Iinuma H, Watanabe T et al (2011) Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with dukes’ stage B and C colorectal cancer. J Clin Oncol 29(12):1547–1555

Ikeguchi M, Kaibara N (2005) Detection of circulating cancer cells after a gastrectomy for gastric cancer. Surg Today 35(6):436–441

Ingber DE (2003) Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci 116(Pt 7):1157–1173

Kajita M, McClinic KN et al (2004) Aberrant expression of the transcription factors snail and slug alters the response to genotoxic stress. Mol Cell Biol 24(17):7559–7566

Kajiyama H, Shibata K et al (2007) Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells. Int J Oncol 31(2):277–283

Kallergi G, Mavroudis D et al (2007) Phosphorylation of FAK, PI-3K, and impaired actin organization in CK-positive micrometastatic breast cancer cells. Mol Med 13(1–2):79–88

Kallergi G, Agelaki S et al (2008) Phosphorylated EGFR and PI3K/Akt signaling kinases are expressed in circulating tumor cells of breast cancer patients. Breast Cancer Res 10(5):R80

Kallergi G, Markomanolaki H et al (2009) Hypoxia-inducible factor-1alpha and vascular endothelial growth factor expression in circulating tumor cells of breast cancer patients. Breast Cancer Res 11(6):R84

Kim MY, Oskarsson T et al (2009) Tumor self-seeding by circulating cancer cells. Cell 139(7):1315–1326

Klein CA, Blankenstein TJ et al (2002) Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet 360(9334):683–689

Koyanagi K, Bilchik AJ et al (2008) Prognostic relevance of occult nodal micrometastases and circulating tumor cells in colorectal cancer in a prospective multicenter trial. Clin Cancer Res 14(22):7391–7396

Krebs MG, Sloane R et al (2011) Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. J Clin Oncol 29(12):1556–1563

Krivacic RT, Ladanyi A et al (2004) A rare-cell detector for cancer. Proc Natl Acad Sci USA 101(29):10501–10504

Lambrechts AC, Bosma AJ et al (1999) Comparison of immunocytochemistry, reverse transcriptase polymerase chain reaction, and nucleic acid sequence-based amplification for the detection of circulating breast cancer cells. Breast Cancer Res Treat 56(3):219–231

Lankiewicz S, Zimmermann S et al (2008) Circulating tumour cells as a predictive factor for response to systemic chemotherapy in patients with advanced colorectal cancer. Mol Oncol 2(4):349–355

Leversha MA, Han J et al (2009) Fluorescence in situ hybridization analysis of circulating tumor cells in metastatic prostate cancer. Clin Cancer Res 15(6):2091–2097

Li G, Passebosc-Faure K et al (2005) Cadherin-6 gene expression in conventional renal cell carcinoma: a useful marker to detect circulating tumor cells. Anticancer Res 25(1A):377–381

Liu MC, Shields PG et al (2009) Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin Oncol 27(31):5153–5159

Lu J, Fan T et al (2010) Isolation of circulating epithelial and tumor progenitor cells with an invasive phenotype from breast cancer patients. Int J Cancer 126(3):669–683

Maheswaran S, Sequist LV et al (2008) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359(4):366–377

Mao X, Shaw G et al (2008) Detection of TMPRSS2:ERG fusion gene in circulating prostate cancer cells. Asian J Androl 10(3):467–473

Marrinucci D, Bethel K et al (2010) Cytomorphology of circulating colorectal tumor cells: a small case series. J Oncol 2010:861341

Matrone MA, Whipple RA et al (2010) Microtentacles tip the balance of cytoskeletal forces in circulating tumor cells. Cancer Res 70(20):7737–7741

Matsusaka S, Suenaga M et al (2011) Circulating tumor cells as a surrogate marker for determining response to chemotherapy in Japanese patients with metastatic colorectal cancer. Cancer Sci 102(6):1188–1192

Matsusaka S, Chin K et al (2010) Circulating tumor cells as a surrogate marker for determining response to chemotherapy in patients with advanced gastric cancer. Cancer Sci 101(4):1067–1071

McShane LM, Altman DG et al (2005) REporting recommendations for tumour MARKer prognostic studies (REMARK). Eur J Cancer 41(12):1690–1696

Monteiro J, Fodde R (2010) Cancer stemness and metastasis: therapeutic consequences and perspectives. Eur J Cancer 46(7):1198–1203

Moreno JG, Miller MC et al (2005) Circulating tumor cells predict survival in patients with metastatic prostate cancer. Urology 65(4):713–718

Nagrath S, Sequist LV et al (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173):1235–1239

Nakagawa T, Martinez SR et al (2007) Detection of circulating tumor cells in early-stage breast cancer metastasis to axillary lymph nodes. Clin Cancer Res 13(14):4105–4110

Nakamura S, Yagata H et al (2010) Multi-center study evaluating circulating tumor cells as a surrogate for response to treatment and overall survival in metastatic breast cancer. Breast Cancer 17(3):199–204

Naoe M, Ogawa Y et al (2007) Detection of circulating urothelial cancer cells in the blood using the CellSearch System. Cancer 109(7):1439–1445

Navin N, Kendall J et al (2011) Tumour evolution inferred by single-cell sequencing. Nature 472(7341):90–94

Negin BP, Cohen SJ (2010) Circulating tumor cells in colorectal cancer: past, present, and future challenges. Curr Treat Options Oncol 11(1–2):1–13

Nezos A, Pissimisis N et al (2009) Detection of circulating tumor cells in bladder cancer patients. Cancer Treat Rev 35(3):272–279

Nolan T, Hands RE et al (2006) Quantification of mRNA using real-time RT-PCR. Nat Protoc 1(3):1559–1582

O’Brien CA, Pollett A et al (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445(7123):106–110

Okegawa T, Nutahara K et al (2009) Prognostic significance of circulating tumor cells in patients with hormone refractory prostate cancer. J Urol 181(3):1091–1097

Olmos D, Arkenau HT et al (2009) Circulating tumour cell (CTC) counts as intermediate end points in castration-resistant prostate cancer (CRPC): a single-centre experience. Ann Oncol 20(1):27–33

Ota I, Li XY et al (2009) Induction of a MT1-MMP and MT2-MMP-dependent basement membrane transmigration program in cancer cells by Snail1. Proc Natl Acad Sci USA 106(48):20318–20323

Pantel K, Brakenhoff RH et al (2008) Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 8(5):329–340

Paris PL, Kobayashi Y et al (2009) Functional phenotyping and genotyping of circulating tumor cells from patients with castration resistant prostate cancer. Cancer Lett 277(2):164–173

Peinado H, Marin F et al (2004) Snail and E47 repressors of E-cadherin induce distinct invasive and angiogenic properties in vivo. J Cell Sci 117(Pt 13):2827–2839

Pestrin M, Bessi S et al (2009) Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients. Breast Cancer Res Treat 118(3):523–530

Pierga JY, Bidard FC et al (2008) Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase II randomized trial. Clin Cancer Res 14(21):7004–7010

Polyak K, Weinberg RA (2009) Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 9(4):265–273

Puisieux A, Valsesia-Wittmann S (2006) Cancer cells escape from failsafe programs in a simple Twist. Bull Cancer 93(3):251–256

Rahbari NN, Aigner M et al (2010) Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology 138(5):1714–1726

Raimondi C, Gradilone A et al (2011) Epithelial-mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients. Breast Cancer Res Treat [Epub ahead of print]

Ring A, Smith IE et al (2004) Circulating tumour cells in breast cancer. Lancet Oncol 5(2):79–88

Ring AE, Zabaglo L et al (2005) Detection of circulating epithelial cells in the blood of patients with breast cancer: comparison of three techniques. Br J Cancer 92(5):906–912

Royston P, Altman DG et al (2006) Dichotomizing continuous predictors in multiple regression: a bad idea. Stat Med 25(1):127–141

Sabbah M, Emami S et al (2008) Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal transitions in epithelial cancers. Drug Resist Updat 11(4–5):123–151

Sayan AE, Griffiths TR et al (2009) SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer. Proc Natl Acad Sci USA 106(35):14884–14889

Sboner A, Demichelis F et al (2010) Molecular sampling of prostate cancer: a dilemma for predicting disease progression. BMC Med Genomics 3:8

Scatton O, Chiappini F et al (2006) Fate and characterization of circulating tumor cells in a NOD/SCID mouse model of human hepatocellular carcinoma. Oncogene 25(29):4067–4075

Scher HI, Jia X et al (2009) Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol 10(3):233–239

Seo JH, Choi CW et al (2005) Follow-up study of peripheral blood carcinoembryonic antigen mRNA using reverse transcription-polymerase chain reaction as an early marker of clinical recurrence in patients with curatively resected gastric cancer. Am J Clin Oncol 28(1):24–29

Serrano MJ, Sanchez-Rovira P et al (2009) Detection of circulating tumor cells in the context of treatment: prognostic value in breast cancer. Cancer Biol Ther 8(8):671–675

Shen C, Hu L et al (2009) The detection of circulating tumor cells of breast cancer patients by using multimarker (Survivin, hTERT and hMAM) quantitative real-time PCR. Clin Biochem 42(3):194–200

Shih JY, Tsai MF et al (2005) Transcription repressor slug promotes carcinoma invasion and predicts outcome of patients with lung adenocarcinoma. Clin Cancer Res 11(22):8070–8078

Shimazui T, Yoshikawa K et al (2003) Detection of cadherin-6 mRNA by nested RT-PCR as a potential marker for circulating cancer cells in renal cell carcinoma. Int J Oncol 23(4):1049–1054

Sieuwerts AM, Mostert B et al (2011) mRNA and microRNA expression profiles in circulating tumor cells and primary tumors of metastatic breast cancer patients. Clin Cancer Res 17(11):3600–3618

Sieuwerts AM, Kraan J et al (2009) Molecular characterization of circulating tumor cells in large quantities of contaminating leukocytes by a multiplex real-time PCR. Breast Cancer Res Treat 118(3):455–468

Silva AL, Tome MJ et al (2002) Human mammaglobin RT-PCR assay for detection of occult breast cancer cells in hematopoietic products. Ann Oncol 13(3):422–429

Sleijfer S, Gratama JW et al (2007) Circulating tumour cell detection on its way to routine diagnostic implementation? Eur J Cancer 43(18):2645–2650

Smit MA, Peeper DS (2011) Zeb1 is required for TrkB-induced epithelial-mesenchymal transition, anoikis resistance and metastasis. Oncogene [Epub ahead of print]

Smit MA, Geiger TR et al (2009) A Twist-Snail axis critical for TrkB-induced epithelial-mesenchymal transition-like transformation, anoikis resistance, and metastasis. Mol Cell Biol 29(13):3722–3737

Stein JP, Lieskovsky G et al (2001) Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 19(3):666–675

Stott SL, Lee RJ et al (2010b) Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer. Sci Transl Med 2(25):25ra23

Stott SL, Hsu CH et al (2010) Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc Natl Acad Sci USA 107(43):18392–18397

Sun T, Zhao N et al (2010) Expression and functional significance of Twist1 in hepatocellular carcinoma: its role in vasculogenic mimicry. Hepatology 51(2):545–556

Swennenhuis JF, Tibbe AG et al (2009) Characterization of circulating tumor cells by fluorescence in situ hybridization. Cytometry A 75(6):520–527

Tan SJ, Yobas L et al (2009) Microdevice for the isolation and enumeration of cancer cells from blood. Biomed Microdevices 11(4):883–892

Tanaka F, Yoneda K et al (2009) Circulating tumor cell as a diagnostic marker in primary lung cancer. Clin Cancer Res 15(22):6980–6986

Tewes M, Aktas B et al (2009) Molecular profiling and predictive value of circulating tumor cells in patients with metastatic breast cancer: an option for monitoring response to breast cancer related therapies. Breast Cancer Res Treat 115(3):581–590

Thiery JP, Sleeman JP (2006) Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 7(2):131–142

Thiery JP, Acloque H et al (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139(5):871–890

Uen YH, Lu CY et al (2008) Persistent presence of postoperative circulating tumor cells is a poor prognostic factor for patients with stage I-III colorectal cancer after curative resection. Ann Surg Oncol 15(8):2120–2128

Van der Auwera I, Peeters D et al (2010) Circulating tumour cell detection: a direct comparison between the CellSearch System, the AdnaTest and CK-19/mammaglobin RT-PCR in patients with metastatic breast cancer. Br J Cancer 102(2):276–284

Vona G, Sabile A et al (2000) Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells. Am J Pathol 156(1):57–63

Vona G, Estepa L et al (2004) Impact of cytomorphological detection of circulating tumor cells in patients with liver cancer. Hepatology 39(3):792–797

Wang L, Wang Y et al (2009) Flow cytometric analysis of CK19 expression in the peripheral blood of breast carcinoma patients: relevance for circulating tumor cell detection. J Exp Clin Cancer Res 28:57

Willipinski-Stapelfeldt B, Riethdorf S et al (2005) Changes in cytoskeletal protein composition indicative of an epithelial-mesenchymal transition in human micrometastatic and primary breast carcinoma cells. Clin Cancer Res 11(22):8006–8014

Wu CH, Lin SR et al (2006) Molecular detection of disseminated tumor cells in the peripheral blood of patients with gastric cancer: evaluation of their prognostic significance. Dis Markers 22(3):103–109

Wu C, Hao H et al (2009) Preliminary investigation of the clinical significance of detecting circulating tumor cells enriched from lung cancer patients. J Thorac Oncol 4(1):30–36

Xi L, Nicastri DG et al (2007) Optimal markers for real-time quantitative reverse transcription PCR detection of circulating tumor cells from melanoma, breast, colon, esophageal, head and neck, and lung cancers. Clin Chem 53(7):1206–1215

Xu W, Cao L et al (2011) Isolation of circulating tumor cells in patients with hepatocellular carcinoma using an asialoglycoprotein receptor-based magnetic cell separation strategy. Clin Cancer Res 17(11):3783–3793

Yagata H, Nakamura S et al (2008) Evaluation of circulating tumor cells in patients with breast cancer: multi-institutional clinical trial in Japan. Int J Clin Oncol 13(3):252–256

Yang AD, Fan F et al (2006) Chronic oxaliplatin resistance induces epithelial-to-mesenchymal transition in colorectal cancer cell lines. Clin Cancer Res 12(14 Pt 1):4147–4153

Yang J, Weinberg RA (2008) Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 14(6):818–829

Yang ZF, Ngai P et al (2008) Identification of local and circulating cancer stem cells in human liver cancer. Hepatology 47(3):919–928

Yie SM, Lou B et al (2008) Detection of survivin-expressing circulating cancer cells (CCCs) in peripheral blood of patients with gastric and colorectal cancer reveals high risks of relapse. Ann Surg Oncol 15(11):3073–3082

You F, Roberts LA et al (2008) Low-level expression of HER2 and CK19 in normal peripheral blood mononuclear cells: relevance for detection of circulating tumor cells. J Hematol Oncol 1:2

Zach O, Kasparu H et al (1999) Detection of circulating mammary carcinoma cells in the peripheral blood of breast cancer patients via a nested reverse transcriptase polymerase chain reaction assay for mammaglobin mRNA. J Clin Oncol 17(7):2015–2019

Zhou H, Guo JM et al (2010) Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using microRNA as a marker. J Mol Med 88(7):709–717