1932

Abstract

Evaluation of circulating tumor cells (CTCs) has demonstrated clinical validity as a prognostic tool based on enumeration, but since the introduction of this tool to the clinic in 2004, further clinical utility and widespread adoption have been limited. However, immense efforts have been undertaken to further the understanding of the mechanisms behind the biology and kinetics of these rare cells, and progress continues toward better applicability in the clinic. This review describes recent advances within the field, with a particular focus on understanding the biological significance of CTCs, and summarizes emerging methods for identifying, isolating, and interrogating the cells that may provide technical advantages allowing for the discovery of more specific clinical applications. Included is an atlas of high-definition images of CTCs from various cancer types, including uncommon CTCs captured only by broadly inclusive nonenrichment techniques.

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2017-01-24
2024-06-25
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Literature Cited

  1. Siegel RL, Miller KD, Jemal A. 1.  2015. Cancer statistics, 2015. CA Cancer J. Clin 65:15–29 [Google Scholar]
  2. Burrell RA, McGranahan N, Bartek J, Swanton C. 2.  2013. The causes and consequences of genetic heterogeneity in cancer evolution. Nature 501:7467338–45 [Google Scholar]
  3. Babayan A, Hannemann J, Spötter J, Müller V, Pantel K, Joosse SA. 3.  2013. Heterogeneity of estrogen receptor expression in circulating tumor cells from metastatic breast cancer patients. PLOS ONE 8:9e75038 [Google Scholar]
  4. Zhang C, Guan Y, Sun Y, Ai D, Guo Q. 4.  2016. Tumor heterogeneity and circulating tumor cells. Cancer Lett 374:2216–23 [Google Scholar]
  5. de Bruin EC, McGranahan N, Mitter R, Salm M, Wedge DC. 5.  et al. 2014. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science 346:6206251–56 [Google Scholar]
  6. Ashworth TR. 6.  1869. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Med. J. Aust 14146–47 [Google Scholar]
  7. Fischer AH. 7.  2009. Circulating tumor cells: Seeing is believing. Arch. Pathol. Lab. Med. 133:91367–69 [Google Scholar]
  8. Miller MC, Doyle GV, Terstappen LWMM. 8.  2010. Significance of circulating tumor cells detected by the CellSearch system in patients with metastatic breast colorectal and prostate cancer. J. Oncol 2010:617421 [Google Scholar]
  9. Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC. 9.  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. 10:206897–904 [Google Scholar]
  10. Marrinucci D, Bethel K, Kolatkar A, Luttgen MS, Malchiodi M. 10.  et al. 2012. Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers. Phys. Biol. 9:1016003 [Google Scholar]
  11. Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D. 11.  et al. 2007. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450:71731235–39 [Google Scholar]
  12. Rack B, Schindlbeck C, Jückstock J, Andergassen U, Hepp P. 12.  et al. 2014. Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J. Natl. Cancer Inst. 106:5dju066 [Google Scholar]
  13. Balic M, Dandachi N, Hofmann G, Samonigg H, Loibner H. 13.  et al. 2005. Comparison of two methods for enumerating circulating tumor cells in carcinoma patients. Cytom. B Clin. Cytom. 68:125–30 [Google Scholar]
  14. Riethdorf S, Fritsche H, Muller V, Rau T, Schindlbeck C. 14.  et al. 2007. Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clin. Cancer Res. 13:3920–28 [Google Scholar]
  15. Drye JC, Rumage WT, Anderson D. 15.  1962. Prognostic import of circulating cancer cells after curative surgery: a long time follow up study. Ann. Surg. 155:733–40 [Google Scholar]
  16. Salsbury AJ. 16.  1975. The significance of the circulating cancer cell. Cancer Treat. Rev. 2:155–72 [Google Scholar]
  17. 17. World Health Organ. (WHO). 1963. Cancer control: first report of an expert committee Tech. Rep. 251, WHO [Google Scholar]
  18. Bao H, Burke PA, Huang J, Chen X, Brohawn PZ. 18.  et al. 2013. Circulating tumor cells: application as a biomarker for molecular characterization and predictor of survival in an all-comer solid tumor Phase I clinical study. PLOS ONE 8:8e58557 [Google Scholar]
  19. Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ. 19.  et al. 2015. Breast Cancer Version 2.2015: clinical practice guidelines in oncology. J. Natl. Compr. Cancer Netw. 13:4448–75 [Google Scholar]
  20. Ruiz C, Li J, Luttgen MS, Kolatkar A, Kendall JT. 20.  et al. 2015. Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients. Phys. Biol. 12:1016008 [Google Scholar]
  21. Chang L, Asatrian G, Dry SM, James AW. 21.  2015. Circulating tumor cells in sarcomas: a brief review. Med. Oncol 321430 [Google Scholar]
  22. Alix-Panabières C, Pantel K. 22.  2016. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov 6:479–91 [Google Scholar]
  23. Pantel K, Alix-Panabières C. 23.  2016. Liquid biopsy: potential and challenges. Mol. Oncol. 10:3371–73 [Google Scholar]
  24. Labelle M, Begum S, Hynes RO. 24.  2011. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell 20:5576–90 [Google Scholar]
  25. Gold B, Cankovic M, Furtado LV, Meier F, Gocke CD. 25.  2015. Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility? A report of the Association for Molecular Pathology. J. Mol. Diagn. 17:3209–24 [Google Scholar]
  26. Newman AM, Bratman SV, To J, Wynne JF, Eclov NCW. 26.  et al. 2014. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat. Med. 20:5548–54 [Google Scholar]
  27. Harouaka RA, Nisic M, Zheng S-Y. 27.  2013. Circulating tumor cell enrichment based on physical properties. J. Lab. Autom. 18:6455–68 [Google Scholar]
  28. Shapiro HM, Schildkraut ER, Curbelo R, Laird CW, Turner B, Hirschfeld T. 28.  1976. Combined blood cell counting and classification with fluorochrome stains and flow instrumentation. J. Histochem. Cytochem. 24:1396–401 [Google Scholar]
  29. Guck J, Schinkinger S, Lincoln B, Wottawah F, Ebert S. 29.  et al. 2005. Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys. J. 88:53689–98 [Google Scholar]
  30. Suresh S. 30.  2007. Biomechanics and biophysics of cancer cells. Acta Biomater 3:4413–38 [Google Scholar]
  31. Park ES, Jin C, Guo Q, Ang RR, Duffy SP. 31.  et al. 2016. Continuous flow deformability-based separation of circulating tumor cells using microfluidic ratchets. Small 12:141909–19 [Google Scholar]
  32. Coughlin MF, Bielenberg DR, Lenormand G, Marinkovic M, Waghorne CG. 32.  et al. 2013. Cytoskeletal stiffness, friction, and fluidity of cancer cell lines with different metastatic potential. Clin. Exp. Metastasis 30:3237–50 [Google Scholar]
  33. Cross SE, Jin Y-S, Rao J, Gimzewski JK. 33.  2007. Nanomechanical analysis of cells from cancer patients. Nat. Nanotechnol. 2:12780–83 [Google Scholar]
  34. Shaw Bagnall J, Byun S, Begum S, Miyamoto DT, Hecht VC. 34.  et al. 2015. Deformability of tumor cells versus blood cells. Sci. Rep. 5:18542 [Google Scholar]
  35. Pethig R. 35.  2010. Dielectrophoresis: status of the theory, technology, and applications. Biomicrofluidics 4:2022811 [Google Scholar]
  36. Gascoyne P, Shim S. 36.  2014. Isolation of circulating tumor cells by dielectrophoresis. Cancers 6:1545–79 [Google Scholar]
  37. Davis D, Gupta V, Garza M, Pace M, Wu W. 37.  et al. 2011. EpCAM-independent ApoStream™ technology isolates circulating tumor cells from blood of patients with various types of cancer. Mol. Cancer Ther. 10:Suppl. 1B20 (Abstr.) [Google Scholar]
  38. Ponder E. 38.  1942. The relation between red blood cell density and corpuscular hemoglobin concentration. J. Biol. Chem. 144:333–38 [Google Scholar]
  39. Phillips KG, Velasco CR, Li J, Kolatkar A, Luttgen M. 39.  et al. 2012. Optical quantification of cellular mass, volume, and density of circulating tumor cells identified in an ovarian cancer patient. Front. Oncol. 2:72 [Google Scholar]
  40. Nadal R, Lorente JA, Rosell R, Serrano MJ. 40.  2013. Relevance of molecular characterization of circulating tumor cells in breast cancer in the era of targeted therapies. Expert Rev. Mol. Diagn. 13:3295–307 [Google Scholar]
  41. Fehm T, Müller V, Aktas B, Janni W, Schneeweiss A. 41.  et al. 2010. Her2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res. Treat. 124:2403–12 [Google Scholar]
  42. Gasch C, Bauernhofer T, Pichler M, Langer-Freitag S, Reeh M. 42.  et al. 2013. Heterogeneity of epidermal growth factor receptor status and mutations of KRAS/PIK3CA in circulating tumor cells of patients with colorectal cancer. Clin. Chem 59:1252–60 [Google Scholar]
  43. Schramm A, Friedl TWP, Schochter F, Scholz C, de Gregorio N. 43.  et al. 2016. Therapeutic intervention based on circulating tumor cell phenotype in metastatic breast cancer: concept of the DETECT study program. Arch. Gynecol. Obstet. 293:2271–81 [Google Scholar]
  44. Gazzaniga P, Raimondi C, Gradilone A, Cortesi E, Naso G. 44.  2014. Clinical utility of circulating tumor cell counting through CellSearch®: the dilemma of a concept suspended in limbo. OncoTargets Ther 7:619–25 [Google Scholar]
  45. Masuda T, Hayashi N, Iguchi T, Ito S, Eguchi H, Mimori K. 45.  2016. Clinical and biological significance of circulating tumor cells in cancer. Mol. Oncol. 10:3408–17 [Google Scholar]
  46. Marrinucci D, Bethel K, Bruce RH, Curry DN, Hsieh B. 46.  et al. 2007. Case study of the morphologic variation of circulating tumor cells. Hum. Pathol. 38:3514–19 [Google Scholar]
  47. Kolostova K, Spicka J, Matkowski R, Bobek V. 47.  2015. Isolation, primary culture, morphological and molecular characterization of circulating tumor cells in gynecological cancers. Am. J. Transl. Res. 7:71203–13 [Google Scholar]
  48. Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO. 48.  et al. 2001. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 61:41659–65 [Google Scholar]
  49. Krebs MG, Metcalf RL, Carter L, Brady G, Blackhall FH, Dive C. 49.  2014. Molecular analysis of circulating tumour cells—biology and biomarkers. Nat. Rev. Clin. Oncol. 11:3129–44 [Google Scholar]
  50. Park S, Ang RR, Duffy SP, Bazov J, Chi KN. 50.  et al. 2014. Morphological differences between circulating tumor cells from prostate cancer patients and cultured prostate cancer cells. PLOS ONE 9:1e85264 [Google Scholar]
  51. Ligthart ST, Coumans FAW, Bidard F-C, Simkens LHJ, Punt CJA. 51.  et al. 2013. Circulating tumor cells count and morphological features in breast, colorectal and prostate cancer. PLOS ONE 8:6e67148 [Google Scholar]
  52. Pantel K, Speicher MR. 52.  2016. The biology of circulating tumor cells. Oncogene 35:101216–24 [Google Scholar]
  53. Cavallaro U, Christofori G. 53.  2001. Cell adhesion in tumor invasion and metastasis: Loss of the glue is not enough. Biochim. Biophys. Acta 1552:139–45 [Google Scholar]
  54. Liotta LA, Kleinerman J, Saidel GM. 54.  1974. Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. Cancer Res 34:5997–1004 [Google Scholar]
  55. Chang YS, di Tomaso E, McDonald DM, Jones R, Jain RK, Munn LL. 55.  2000. Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. PNAS 97:2614608–13 [Google Scholar]
  56. Condeelis J, Pollard JW. 56.  2006. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124:2263–66 [Google Scholar]
  57. Bockhorn M, Jain RK, Munn LL. 57.  2007. Active versus passive mechanisms in metastasis: Do cancer cells crawl into vessels, or are they pushed?. Lancet Oncol 8:5444–48 [Google Scholar]
  58. Kalluri R, Weinberg RA. 58.  2009. The basics of epithelial-mesenchymal transition. J. Clin. Investig. 119:61420–28 [Google Scholar]
  59. Pietilä M, Ivaska J, Mani SA. 59.  2016. Whom to blame for metastasis, the epithelial-mesenchymal transition or the tumor microenvironment?. Cancer Lett 380:1359–68 [Google Scholar]
  60. Laberge R-M, Awad P, Campisi J, Desprez P-Y. 60.  2012. Epithelial-mesenchymal transition induced by senescent fibroblasts. Cancer Microenviron 5:139–44 [Google Scholar]
  61. Liu Z-J, Semenza GL, Zhang H-F. 61.  2015. Hypoxia-inducible factor 1 and breast cancer metastasis. J. Zhejiang Univ. Sci. B 16:132–43 [Google Scholar]
  62. Bacigalupo ML, Manzi M, Espelt MV, Gentilini LD, Compagno D. 62.  et al. 2015. Galectin-1 triggers epithelial-mesenchymal transition in human hepatocellular carcinoma cells. J. Cell. Physiol. 230:61298–309 [Google Scholar]
  63. Mamuya FA, Duncan MK. 63.  2012. αV integrins and TGF-β-induced EMT: a circle of regulation. J. Cell. Mol. Med. 16:3445–55 [Google Scholar]
  64. Hazan RB, Qiao R, Keren R, Badano I, Suyama K. 64.  2004. Cadherin switch in tumor progression. Ann. N. Y. Acad. Sci. 1014:155–63 [Google Scholar]
  65. Martin TA, Ye L, Sanders AJ, Lane J, Jiang WG. 65.  2013. Cancer invasion and metastasis: molecular and cellular perspective. Metastatic Cancer: Clinical and Biological Perspectives R Jandial Austin: Landes Biosci. [Google Scholar]
  66. Chang JT, Mani SA. 66.  2013. Sheep, wolf, or werewolf: cancer stem cells and the epithelial-to-mesenchymal transition. Cancer Lett 341:116–23 [Google Scholar]
  67. Shibue T, Brooks MW, Weinberg RA. 67.  2013. An integrin-linked machinery of cytoskeletal regulation that enables experimental tumor initiation and metastatic colonization. Cancer Cell 24:4481–98 [Google Scholar]
  68. Sleeman JP, Thiery JP. 68.  2011. SnapShot: the epithelial-mesenchymal transition. Cell 145:1162.e1 [Google Scholar]
  69. Clark AG, Vignjevic DM. 69.  2015. Modes of cancer cell invasion and the role of the microenvironment. Curr. Opin. Cell Biol. 36:13–22 [Google Scholar]
  70. Ueno H, Shinto E, Kajiwara Y, Fukazawa S, Shimazaki H. 70.  et al. 2014. Prognostic impact of histological categorisation of epithelial-mesenchymal transition in colorectal cancer. Br. J. Cancer 111:112082–90 [Google Scholar]
  71. Kohler I, Bronsert P, Timme S, Werner M, Brabletz T. 71.  et al. 2015. Detailed analysis of epithelial-mesenchymal transition and tumor budding identifies predictors of long-term survival in pancreatic ductal adenocarcinoma. J. Gastroenterol. Hepatol. 30:Suppl. 178–84 [Google Scholar]
  72. Stewart CJR, McCluggage WG. 72.  2013. Epithelial-mesenchymal transition in carcinomas of the female genital tract. Histopathology 62:131–43 [Google Scholar]
  73. Tsuji T, Ibaragi S, Hu G-F. 73.  2009. Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res 69:187135–39 [Google Scholar]
  74. Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS. 74.  et al. 2014. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158:51110–22 [Google Scholar]
  75. Fischer KR, Durrans A, Lee S, Sheng J, Li F. 75.  et al. 2015. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature 527:7579472–76 [Google Scholar]
  76. Zheng X, Carstens JL, Kim J, Scheible M, Kaye J. 76.  et al. 2015. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature 527:7579525–30 [Google Scholar]
  77. Frisch SM, Francis H. 77.  1994. Disruption of epithelial cell-matrix interactions induces apoptosis. J. Cell Biol. 124:4619–26 [Google Scholar]
  78. Bockhorn M, Roberge S, Sousa C, Jain RK, Munn LL. 78.  2004. Differential gene expression in metastasizing cells shed from kidney tumors. Cancer Res 64:72469–73 [Google Scholar]
  79. Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ. 79.  et al. 2004. Circulating tumor cells in patients with breast cancer dormancy. Clin. Cancer Res. 10:8152–62 [Google Scholar]
  80. Rossi E, Basso U, Celadin R, Zilio F, Pucciarelli S. 80.  et al. 2010. M30 neoepitope expression in epithelial cancer: quantification of apoptosis in circulating tumor cells by CellSearch analysis. Clin. Cancer Res. 16:215233–43 [Google Scholar]
  81. Cho EH, Wendel M, Luttgen M, Yoshioka C, Marrinucci D. 81.  et al. 2012. Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors. Phys. Biol. 9:1016001 [Google Scholar]
  82. Kats-Ugurlu G, Roodink I, de Weijert M, Tiemessen D, Maass C. 82.  et al. 2009. Circulating tumour tissue fragments in patients with pulmonary metastasis of clear cell renal cell carcinoma. J. Pathol. 219:3287–93 [Google Scholar]
  83. Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. 83.  2007. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J. Thromb. Haemost. 5:3632–34 [Google Scholar]
  84. Shiao SL, Chu GC-Y, Chung LWK. 84.  2016. Regulation of prostate cancer progression by the tumor microenvironment. Cancer Lett 380:1340–48 [Google Scholar]
  85. Zhang J, Qiao X, Shi H, Han X, Liu W. 85.  et al. 2016. Circulating tumor-associated neutrophils (cTAN) contribute to circulating tumor cell survival by suppressing peripheral leukocyte activation. Tumour Biol 37:45397–404 [Google Scholar]
  86. Yadav A, Kumar B, Yu J-G, Old M, Teknos TN, Kumar P. 86.  2015. Tumor-associated endothelial cells promote tumor metastasis by chaperoning circulating tumor cells and protecting them from anoikis. PLOS ONE 10:10e0141602 [Google Scholar]
  87. Liotta LA, Saidel MG, Kleinerman J. 87.  1976. The significance of hematogenous tumor cell clumps in the metastatic process. Cancer Res 36:3889–94 [Google Scholar]
  88. Hou J-M, Krebs MG, Lancashire L, Sloane R, Backen A. 88.  et al. 2012. Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J. Clin. Oncol. 30:5525–32 [Google Scholar]
  89. Yu JL, May L, Lhotak V, Shahrzad S, Shirasawa S. 89.  et al. 2005. Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. Blood 105:41734–41 [Google Scholar]
  90. Phillips KG, Lee AM, Tormoen GW, Rigg RA, Kolatkar A. 90.  et al. 2015. The thrombotic potential of circulating tumor microemboli: computational modeling of circulating tumor cell–induced coagulation. Am. J. Physiol. Cell Physiol. 308:3C229–36 [Google Scholar]
  91. Mitrugno A, Tormoen GW, Kuhn P, McCarty OJT. 91.  2016. The prothrombotic activity of cancer cells in the circulation. Blood Rev 30:111–19 [Google Scholar]
  92. Zhe X, Cher ML, Bonfil RD. 92.  2011. Circulating tumor cells: finding the needle in the haystack. Am. J. Cancer Res. 1:6740–51 [Google Scholar]
  93. Xu L, Shamash J, Lu Y-J. 93.  2015. Circulating tumor cells: a window to understand cancer metastasis, monitor and fight against cancers. J. Cancer Res. Updat. 4:113–29 [Google Scholar]
  94. Duda DG, Duyverman AMMJ, Kohno M, Snuderl M, Steller EJA. 94.  et al. 2010. Malignant cells facilitate lung metastasis by bringing their own soil. PNAS 107:5021677–82 [Google Scholar]
  95. Norton L, Massagué J. 95.  2006. Is cancer a disease of self-seeding?. Nat. Med. 12:8875–78 [Google Scholar]
  96. Paget S. 96.  1989. The distribution of secondary growths in cancer of the breast. Cancer Metastasis Rev 8:298–101 [Google Scholar]
  97. Comen E, Norton L, Massagué J. 97.  2011. Clinical implications of cancer self-seeding. Nat. Rev. Clin. Oncol. 8:6369–77 [Google Scholar]
  98. Pattabiraman DR, Bierie B, Kober KI, Thiru P, Krall JA. 98.  et al. 2016. Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability. Science 351:6277aad3680 [Google Scholar]
  99. Yao D, Dai C, Peng S. 99.  2011. Mechanism of the mesenchymal-epithelial transition and its relationship with metastatic tumor formation. Mol. Cancer Res. 9:121608–20 [Google Scholar]
  100. Massagué J, Obenauf AC. 100.  2016. Metastatic colonization by circulating tumour cells. Nature 529:7586298–306 [Google Scholar]
  101. Kim M-Y, Oskarsson T, Acharyya S, Nguyen DX, Zhang XH-F. 101.  et al. 2009. Tumor self-seeding by circulating cancer cells. Cell 139:71315–26 [Google Scholar]
  102. Newton PK, Mason J, Bethel K, Bazhenova L, Nieva J. 102.  et al. 2013. Spreaders and sponges define metastasis in lung cancer: a Markov chain Monte Carlo mathematical model. Cancer Res 73:92760–69 [Google Scholar]
  103. Chaffer CL, Weinberg RA. 103.  2011. A perspective on cancer cell metastasis. Science 331:60241559–64 [Google Scholar]
  104. Spiliotaki M, Mavroudis D, Kapranou K, Markomanolaki H, Kallergi G. 104.  et al. 2014. Evaluation of proliferation and apoptosis markers in circulating tumor cells of women with early breast cancer who are candidates for tumor dormancy. Breast Cancer Res 16:6485 [Google Scholar]
  105. McGovern M, Voutev R, Maciejowski J, Corsi AK, Hubbard EJA. 105.  2009. A “latent niche” mechanism for tumor initiation. PNAS 106:2811617–22 [Google Scholar]
  106. Yeh AC, Ramaswamy S. 106.  2015. Mechanisms of cancer cell dormancy—another hallmark of cancer?. Cancer Res 75:235014–22 [Google Scholar]
  107. Joosse SA, Gorges TM, Pantel K. 107.  2015. Biology, detection, and clinical implications of circulating tumor cells. EMBO Mol. Med. 7:11–11 [Google Scholar]
  108. Alix-Panabières C, Pantel K. 108.  2014. Challenges in circulating tumour cell research. Nat. Rev. Cancer 14:9623–31 [Google Scholar]
  109. Harouaka R, Kang Z, Zheng S-Y, Cao L. 109.  2014. Circulating tumor cells: advances in isolation and analysis, and challenges for clinical applications. Pharmacol. Ther. 141:2209–21 [Google Scholar]
  110. Cristofanilli M, Hayes DF, Budd GT, Ellis MJ, Stopeck A. 110.  et al. 2005. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J. Clin. Oncol. 23:71420–30 [Google Scholar]
  111. Stott SL, Hsu C-H, Tsukrov DI, Yu M, Miyamoto DT. 111.  et al. 2010. Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. PNAS 107:4318392–97 [Google Scholar]
  112. Wang S, Thomas A, Lee E, Yang S, Cheng X, Liu Y. 112.  2016. Highly efficient and selective isolation of rare tumor cells using a microfluidic chip with wavy-herringbone micro-patterned surfaces. Analyst 141:2228–37 [Google Scholar]
  113. Wang S, Liu K, Liu J, Yu ZT-F, Xu X. 113.  et al. 2011. Highly efficient capture of circulating tumor cells by using nanostructured silicon substrates with integrated chaotic micromixers. Angew. Chem. Int. Ed. 50:133084–88 [Google Scholar]
  114. Talasaz AH, Powell AA, Huber DE, Berbee JG, Roh K-H. 114.  et al. 2009. Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. PNAS 106:103970–75 [Google Scholar]
  115. Cann GM, Gulzar ZG, Cooper S, Li R, Luo S. 115.  et al. 2012. mRNA-Seq of single prostate cancer circulating tumor cells reveals recapitulation of gene expression and pathways found in prostate cancer. PLOS ONE 7:11e49144 [Google Scholar]
  116. Saucedo-Zeni N, Mewes S, Niestroj R, Gasiorowski L, Murawa D. 116.  et al. 2012. A novel method for the in vivo isolation of circulating tumor cells from peripheral blood of cancer patients using a functionalized and structured medical wire. Int. J. Oncol. 41:41241–50 [Google Scholar]
  117. Gorges TM, Penkalla N, Schalk T, Joosse SA, Riethdorf S. 117.  et al. 2016. Enumeration and molecular characterization of tumor cells in lung cancer patients using a novel in vivo device for capturing circulating tumor cells. Clin. Cancer Res. 22:92197–206 [Google Scholar]
  118. Gorges TM, Tinhofer I, Drosch M, Röse L, Zollner TM. 118.  et al. 2012. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer 12:178 [Google Scholar]
  119. Baker MK, Mikhitarian K, Osta W, Callahan K, Hoda R. 119.  et al. 2003. Molecular detection of breast cancer cells in the peripheral blood of advanced-stage breast cancer patients using multimarker real-time reverse transcription-polymerase chain reaction and a novel porous barrier density gradient centrifugation technology. Clin. Cancer Res. 9:134865–71 [Google Scholar]
  120. Chinen LTD, de Carvalho FM, Rocha BMM, Aguiar CM, Abdallah EA. 120.  et al. 2013. Cytokeratin-based CTC counting unrelated to clinical follow up. J. Thorac. Dis. 5:5593–99 [Google Scholar]
  121. Tan SJ, Yobas L, Lee GYH, Ong CN, Lim CT. 121.  2009. Microdevice for the isolation and enumeration of cancer cells from blood. Biomed. Microdevices 114883–92 [Google Scholar]
  122. Hou HW, Warkiani ME, Khoo BL, Li ZR, Soo RA. 122.  et al. 2013. Isolation and retrieval of circulating tumor cells using centrifugal forces. Sci. Rep. 3:1259 [Google Scholar]
  123. Yin J, Wang Y, Yin H, Chen W, Jin G. 123.  et al. 2015. Circulating tumor cells enriched by the depletion of leukocytes with bi-antibodies in non–small cell lung cancer: potential clinical application. PLOS ONE 10:8e0137076 [Google Scholar]
  124. Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A. 124.  et al. 2013. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat. Biotechnol. 31:6539–44 [Google Scholar]
  125. Alix-Panabières C. 125.  2012. EPISPOT assay: detection of viable DTCs/CTCs in solid tumor patients. Minimal Residual Disease and Circulating Tumor Cells in Breast Cancer. Recent Results in Cancer Research, Volume 195 M Ignatiadis, C Sotiriou, K Pantel 69–76 Berlin/Heidelberg, Ger: Springer [Google Scholar]
  126. Ramirez J-M, Fehm T, Orsini M, Cayrefourcq L, Maudelonde T. 126.  et al. 2014. Prognostic relevance of viable circulating tumor cells detected by EPISPOT in metastatic breast cancer patients. Clin. Chem. 60:1214–21 [Google Scholar]
  127. Pizon M, Zimon D, Carl S, Pachmann U, Pachmann K, Camara O. 127.  2013. Heterogeneity of circulating epithelial tumour cells from individual patients with respect to expression profiles and clonal growth (sphere formation) in breast cancer. ecancermedicalscience 7:343 [Google Scholar]
  128. Wu S, Liu S, Liu Z, Huang J, Pu X. 128.  et al. 2015. Classification of circulating tumor cells by epithelial-mesenchymal transition markers. PLOS ONE 10:4e0123976 [Google Scholar]
  129. Ma Y, Hao S, Wang S, Zhao Y, Lim B. 129.  et al. 2015. A combinatory strategy for detection of live CTCs using microfiltration and a new telomerase-selective adenovirus. Mol. Cancer Ther. 14:3835–43 [Google Scholar]
  130. Zamay GS, Kolovskaya OS, Zamay TN, Glazyrin YE, Krat AV. 130.  et al. 2015. Aptamers selected to postoperative lung adenocarcinoma detect circulating tumor cells in human blood. Mol. Ther. 23:91486–96 [Google Scholar]
  131. Desitter I, Guerrouahen BS, Benali-Furet N, Wechsler J, Jänne PA. 131.  et al. 2011. A new device for rapid isolation by size and characterization of rare circulating tumor cells. Anticancer Res 31:2427–41 [Google Scholar]
  132. Fernandez SV, Bingham C, Fittipaldi P, Austin L, Palazzo J. 132.  et al. 2014. TP53 mutations detected in circulating tumor cells present in the blood of metastatic triple negative breast cancer patients. Breast Cancer Res 16:5445 [Google Scholar]
  133. Fabbri F, Carloni S, Zoli W, Ulivi P, Gallerani G. 133.  et al. 2013. Detection and recovery of circulating colon cancer cells using a dielectrophoresis-based device: KRAS mutation status in pure CTCs. Cancer Lett 335:1225–31 [Google Scholar]
  134. Nieva J, Wendel M, Luttgen MS, Marrinucci D, Bazhenova L. 134.  et al. 2012. High-definition imaging of circulating tumor cells and associated cellular events in non–small cell lung cancer patients: a longitudinal analysis. Phys. Biol. 9:1016004 [Google Scholar]
  135. Williams ES, Rodriguez-Bravo V, Chippada-Venkata U, De Ia Iglesia–Vicente J, Gong Y. 135.  et al. 2015. Generation of prostate cancer patient derived xenograft models from circulating tumor cells. J. Vis. Exp. 104:e53182 [Google Scholar]
  136. Khoo BL, Lee SC, Kumar P, Tan TZ, Warkiani ME. 136.  et al. 2015. Short-term expansion of breast circulating cancer cells predicts response to anti-cancer therapy. Oncotarget 6:1715578–93 [Google Scholar]
  137. Yu M, Bardia A, Aceto N, Bersani F, Madden MW. 137.  et al. 2014. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 345:6193216–20 [Google Scholar]
  138. Hart CD, Galardi F, Pestrin M, De Luca F, Risi E, Di Leo A. 138.  2016. Using CTCs for pharmacogenomic analysis. Pharmacol. Res. 106:92–100 [Google Scholar]
  139. Metzker ML. 139.  2010. Sequencing technologies—the next generation. Nat. Rev. Genet. 11:131–46 [Google Scholar]
  140. Baslan T, Hicks J. 140.  2014. Single cell sequencing approaches for complex biological systems. Curr. Opin. Genet. Dev. 26:59–65 [Google Scholar]
  141. Dean FB, Hosono S, Fang L, Wu X, Faruqi AF. 141.  et al. 2002. Comprehensive human genome amplification using multiple displacement amplification. PNAS 99:85261–66 [Google Scholar]
  142. Polzer B, Medoro G, Pasch S, Fontana F, Zorzino L. 142.  et al. 2014. Molecular profiling of single circulating tumor cells with diagnostic intention. EMBO Mol. Med. 6:111371–86 [Google Scholar]
  143. Heitzer E, Auer M, Gasch C, Pichler M, Ulz P. 143.  et al. 2013. Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing. Cancer Res 73:102965–75 [Google Scholar]
  144. Dago AE, Stepansky A, Carlsson A, Luttgen M, Kendall J. 144.  et al. 2014. Rapid phenotypic and genomic change in response to therapeutic pressure in prostate cancer inferred by high content analysis of single circulating tumor cells. PLOS ONE 9:8e101777 [Google Scholar]
  145. Gasch C, Plummer PN, Jovanovic L, McInnes LM, Wescott D. 145.  et al. 2015. Heterogeneity of miR-10b expression in circulating tumor cells. Sci. Rep. 5:15980 [Google Scholar]
  146. Steinestel J, Luedeke M, Arndt A, Schnoeller TJ, Lennerz JK. 146.  et al. 2016. Detecting predictive androgen receptor modifications in circulating prostate cancer cells. Oncotarget In press [Google Scholar]
  147. Riethdorf S, Müller V, Zhang L, Rau T, Loibl S. 147.  et al. 2010. Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin. Cancer Res. 16:92634–45 [Google Scholar]
  148. Miyamoto DT, Lee RJ, Stott SL, Ting DT, Wittner BS. 148.  et al. 2012. Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer. Cancer Discov 2:11995–1003 [Google Scholar]
  149. Kasimir-Bauer S, Bittner A-K, König L, Reiter K, Keller T. 149.  et al. 2016. Does primary neoadjuvant systemic therapy eradicate minimal residual disease? Analysis of disseminated and circulating tumor cells before and after therapy. Breast Cancer Res 18:120 [Google Scholar]
  150. Fehm T, Becker S, Duerr-Stoerzer S, Sotlar K, Mueller V. 150.  et al. 2007. Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status. Breast Cancer Res 9:5R74 [Google Scholar]
  151. Cho WCS. 151.  2014. Emerging techniques in molecular detection of circulating tumor cells. Expert Rev. Mol. Diagn. 14:2131–34 [Google Scholar]
  152. Moreno JG, O'Hara SM, Gross S, Doyle G, Fritsche H. 152.  et al. 2001. Changes in circulating carcinoma cells in patients with metastatic prostate cancer correlate with disease status. Urology 58:3386–92 [Google Scholar]
  153. Pailler E, Adam J, Barthélémy A, Oulhen M, Auger N. 153.  et al. 2013. Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non-small-cell lung cancer. J. Clin. Oncol. 31:182273–81 [Google Scholar]
  154. Pailler E, Auger N, Lindsay CR, Vielh P, Islas-Morris-Hernandez A. 154.  et al. 2015. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer. Ann. Oncol. 26:71408–15 [Google Scholar]
  155. Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M. 155.  et al. 2014. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N. Engl. J. Med. 371:111028–38 [Google Scholar]
  156. Antonarakis ES, Lu C, Luber B, Wang H, Chen Y. 156.  et al. 2015. Androgen receptor splice variant 7 and efficacy of taxane chemotherapy in patients with metastatic castration-resistant prostate cancer. JAMA Oncol 1:5582–91 [Google Scholar]
  157. Wallwiener M, Riethdorf S, Hartkopf AD, Modugno C, Nees J. 157.  et al. 2014. Serial enumeration of circulating tumor cells predicts treatment response and prognosis in metastatic breast cancer: a prospective study in 393 patients. BMC Cancer 14:512 [Google Scholar]
  158. Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland-Jones B. 158.  et al. 2014. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J. Clin. Oncol. 32:313483–89 [Google Scholar]
  159. Thalgott M, Rack B, Horn T, Heck MM, Eiber M. 159.  et al. 2015. Detection of circulating tumor cells in locally advanced high-risk prostate cancer during neoadjuvant chemotherapy and radical prostatectomy. Anticancer Res 35:105679–85 [Google Scholar]
  160. Gazzaniga P, de Berardinis E, Raimondi C, Gradilone A, Busetto GM. 160.  et al. 2014. Circulating tumor cells detection has independent prognostic impact in high-risk non-muscle invasive bladder cancer. Int. J. Cancer 135:81978–82 [Google Scholar]
  161. He W, Wang H, Hartmann LC, Cheng J-X, Low PS. 161.  2007. In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry. PNAS 104:2811760–65 [Google Scholar]
  162. Li J, Sharkey CC, Wun B, Liesveld J, King MR. 162.  2016. Genetic engineering of platelets to neutralize circulating tumor cells. J. Control. Release 228:38–47 [Google Scholar]
  163. Langenbeck B. 163.  1841. On the development of cancer in the veins. Edinb. Med. Surg. J 55251–53 [Google Scholar]
  164. Engell HC. 164.  1955. Cancer cells in the circulating blood; a clinical study on the occurrence of cancer cells in the peripheral blood and in venous blood draining the tumour area at operation. Acta Chir. Scand. Suppl. 201:1–70 [Google Scholar]
  165. Seal SH. 165.  1959. Silicone flotation: a simple quantitative method for the isolation of free-floating cancer cells from the blood. Cancer 12:3590–95 [Google Scholar]
  166. Alexander RF, Spriggs AI. 166.  1960. The differential diagnosis of tumour cells in circulating blood. J. Clin. Pathol. 13:414–24 [Google Scholar]
  167. Song MJ, Kornatowski G, Parsons DF, King MV. 167.  1987. Detection and characterization of circulating rat mammary tumor cells in buffy coat and correlation with metastasis. Cancer Investig 5:5429–41 [Google Scholar]
  168. Schlimok G, Funke I, Holzmann B, Göttlinger G, Schmidt G. 168.  et al. 1987. Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies. PNAS 84:238672–76 [Google Scholar]
  169. Hardingham JE, Kotasek D, Farmer B, Butler RN, Mi JX. 169.  et al. 1993. Immunobead-PCR: a technique for the detection of circulating tumor cells using immunomagnetic beads and the polymerase chain reaction. Cancer Res 53:153455–58 [Google Scholar]
  170. Racila E, Euhus D, Weiss AJ, Rao C, McConnell J. 170.  et al. 1998. Detection and characterization of carcinoma cells in the blood. PNAS 95:84589–94 [Google Scholar]
  171. Vona G, Sabile A, Louha M, Sitruk V, Romana S. 171.  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. 156:157–63 [Google Scholar]
  172. Krivacic RT, Ladanyi A, Curry DN, Hsieh HB, Kuhn P. 172.  et al. 2004. A rare-cell detector for cancer. PNAS 101:2910501–4 [Google Scholar]
  173. O'Hara SM, Moreno JG, Zweitzig DR, Gross S, Gomella LG, Terstappen LWMM. 173.  2004. Multigene reverse transcription–PCR profiling of circulating tumor cells in hormone-refractory prostate cancer. Clin. Chem. 50:5826–35 [Google Scholar]
  174. Marrinucci D, Bethel K, Lazar D, Fisher J, Huynh E. 174.  et al. 2010. Cytomorphology of circulating colorectal tumor cells: a small case series. J. Oncol. 2010:1–7 [Google Scholar]
  175. Hodgkinson CL, Morrow CJ, Li Y, Metcalf RL, Rothwell DG. 175.  et al. 2014. Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nat. Med. 20:8897–903 [Google Scholar]
  176. Tulley S, Zhao Q, Dong H, Pearl ML, Chen W-T. 176.  2016. Vita-AssayTM method of enrichment and identification of circulating cancer cells/circulating tumor cells (CTCs). Methods Mol. Biol. 1406:107–19 [Google Scholar]
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