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Affinity-Based Enrichment of Circulating Tumor Cells

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Circulating Tumor Cells

Part of the book series: Current Cancer Research ((CUCR))

Abstract

Study of CTC in cancer has always been hampered by its rare existence in blood. In this chapter, we discuss one of first principles employed to capture CTC from cancer patients’ peripheral blood—the affinity-based enrichment of CTC. We briefly discuss the different technologies utilizing antibodies to capture CTC based on specific antigen expression. Then we address the downstream molecular and functional characterization of CTC by utilizing these technologies. We also discuss the limitations of affinity-based CTC enrichment.

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References

  1. Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Hayes DF (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351(8):781–791

    Article  CAS  PubMed  Google Scholar 

  2. Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, Meropol NJ (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

    Article  PubMed  Google Scholar 

  3. de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, Raghavan D (2008) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14(19):6302–6309

    Article  PubMed  Google Scholar 

  4. Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, Haber DA (2008) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359(4):366–377

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Terstappen LW (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

    Article  PubMed  Google Scholar 

  6. Talasaz AH, Powell AA, Huber DE, Berbee JG, Roh KH, Yu W, Davis RW (2009) Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. Proc Natl Acad Sci U S A 106(10):3970–3975

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Toner M (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173):1235–1239

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Stott SL, Hsu CH, Tsukrov DI, Yu M, Miyamoto DT, Waltman BA, Toner M (2010) Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc Natl Acad Sci U S A 107(43):18392–18397

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Hou JM, Krebs MG, Lancashire L, Sloane R, Backen A, Swain RK, Dive C (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(5):525–532

    Article  PubMed  Google Scholar 

  10. Ozkumur E, Shah AM, Ciciliano JC, Emmink BL, Miyamoto DT, Brachtel E, Toner M (2013) Inertial focusing for tumor antigen-dependent and -independent sorting of rare circulating tumor cells. Sci Transl Med 5(179):179ra47

    Article  PubMed Central  PubMed  Google Scholar 

  11. Kirby BJ, Jodari M, Loftus MS, Gakhar G, Pratt ED, Chanel-Vos C, Giannakakou P (2012) Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device. PLoS One 7(4):e35976

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Galletti G, Sung MS, Vahdat LT, Shah MA, Santana SM, Altavilla G, Kirby BJ, Giannakakou P (2014) Isolation of breast cancer and gastric cancer circulating tumor cells by use of an anti HER2-based microfluidic device. Lab Chip 14(1):147–156

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Thege FI, Lannin TB, Saha TN, Tsai S, Kochman ML, Hollingsworth MA, Kirby BJ (2014) Microfluidic immunocapture of circulating pancreatic cells using parallel EpCAM and MUC1 capture characterization, optimization and downstream analysis. Lab Chip 14(10):1775–1784

    Article  CAS  PubMed  Google Scholar 

  14. Zhu B, Smith J, Yarmush ML, Nahmias Y, Kirby BJ, Murthy SK (2013) Microfluidic enrichment of mouse epidermal stem cells and validation of stem cell proliferation in vitro. Tissue Eng Part C Methods 19(10):765–773

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Lu YT, Zhao L, Shen Q, Garcia MA, Wu D, Hou S et al (2013) NanoVelcro Chip for CTC enumeration in prostate cancer patients. Methods 64(2):144–152

    Article  CAS  PubMed  Google Scholar 

  16. Hou S, Zhao H, Zhao L, Shen Q, Wei KS, Suh DY, Yu HH (2013) Capture and stimulated release of circulating tumor cells on polymer-grafted silicon nanostructures. Adv Mater 25(11):1547–1551

    Google Scholar 

  17. Yoon HJ, Kim TH, Zhang Z, Azizi E, Pham TM, Paoletti C, Nagrath S (2013) Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets. Nat Nanotechnol 8(10):735–741

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Casavant BP, Guckenberger DJ, Berry SM, Tokar JT, Lang JM, Beebe DJ (2013) The VerIFAST an integrated method for cell isolation and extracellular/intracellular staining. Lab Chip 13(3):391–396

    Article  CAS  PubMed  Google Scholar 

  19. Shi G, Cui W, Benchimol M, Liu YT, Mattrey RF, Mukthavaram R, Simberg D (2013) Isolation of rare tumor cells from blood cells with buoyant immuno-microbubbles. PLoS One 8(3):e58017

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Saucedo-Zeni N, Mewes S, Niestroj R, Gasiorowski L, Murawa D, Nowaczyk P, Lücke K (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(4):1241–1250

    PubMed Central  PubMed  Google Scholar 

  21. Smerage JB, Barlow WE, Hayes DF, Winer EP, Leyland-Jones B, Srkalovic G, Hortobagyi GN (2013) Abstract S5-07 SWOG S0500—a randomized phase III trial to test the strategy of changing therapy versus maintaining therapy for metastatic breast cancer patients who have elevated circulating tumor cell (CTC) levels at first follow-up assessment. Cancer Res 73(24 Suppl):S05–S07

    Google Scholar 

  22. van’t Veer LJ, Dai H, Van De Vijver MJ, He YD, Hart AA, Mao M et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415(6871):530–536

    Article  Google Scholar 

  23. Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K et al (2004) Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci U S A 101(3):811–816

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Wang Y, Jatkoe T, Zhang Y, Mutch MG, Talantov D, Jiang J et al (2004) Gene expression profiles and molecular markers to predict recurrence of Dukes’ B colon cancer. J Clin Oncol 22(9):1564–1571

    Article  CAS  PubMed  Google Scholar 

  25. Yu M, Ting DT, Stott SL, Wittner BS, Ozsolak F, Paul S et al (2012) RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis. Nature 487(7408):510–513

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Powell AA, Talasaz AH, Zhang H, Coram MA, Reddy A, Deng G et al (2012) Single cell profiling of circulating tumor cells transcriptional heterogeneity and diversity from breast cancer cell lines. PLoS One 7(5):e33788

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Lowes LE, Hedley BD, Keeney M, Allan AL (2012) User-defined protein marker assay development for characterization of circulating tumor cells using the Cell Search® system. Cytometry A 81(11):983–995

    Google Scholar 

  28. Janssen Diagnostics, LLC; Janssen Diagnostics, LLC. Characterization of circulating tumor cells (CTC) from patients with metastatic breast cancer using the CTC-Endocrine Therapy Index (COMETI P2). In ClinicalTrials.gov [Internet]. Bethesda (MD) National Library of Medicine (US). 2012- [cited 2014 June 18]. Available from http//www.clinicaltrials.gov/ct2/show/NCT01701050 NLM Identifier NCT01701050

    Google Scholar 

  29. Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P et al (2014) Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat Biotechnol 32(5):479–484

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Ni X, Zhuo M, Su Z, Duan J, Gao Y, Wang Z et al (2013) Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients. Proc Natl Acad Sci U S A 110(52):21083–21088

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Yu M, Bardia A, Aceto N, Bersani F, Madden MW, Donaldson MC et al (2014) Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 345(6193):216–220

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Zhang L, Ridgway LD, Wetzel MD, Ngo J, Yin W, Kumar D et al (2013) The identification and characterization of breast cancer CTCs competent for brain metastasis. Sci Transl Med 5(180):180ra48

    Article  PubMed  Google Scholar 

  33. Deng G, Herrler M, Burgess D, Manna E, Krag D, Burke JF (2008) Enrichment with anti-cytokeratin alone or combined with anti-EpCAM antibodies significantly increases the sensitivity for circulating tumor cell detection in metastatic breast cancer patients. Breast Cancer Res 10(4):R69

    Article  PubMed Central  PubMed  Google Scholar 

  34. Gorges TM, Tinhofer I, Drosch M, Röse L, Zollner TM, Krahn T, von Ahsen O (2012) Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer 12(1):178

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Antolovic D, Galindo L, Carstens A, Rahbari N, BĂĽchler MW, Weitz J, Koch M (2010) Heterogeneous detection of circulating tumor cells in patients with colorectal cancer by immunomagnetic enrichment using different EpCAM-specific antibodies. BMC Biotechnol 10(1):35

    Article  PubMed Central  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA

    Zheng Ao Ph.D.

  2. Department of Pathology & Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL, 33136, USA

    Richard J. Cote M.D., F.R.C.Path., F.C.A.P. & Ram H. Datar M.Phil., Ph.D.

  3. Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA

    Richard J. Cote M.D., F.R.C.Path., F.C.A.P. & Ram H. Datar M.Phil., Ph.D.

  4. Department of Pathology, Jackson Memorial Hospital, Miami, FL, USA

    Richard J. Cote M.D., F.R.C.Path., F.C.A.P.

  5. Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute, University of Miami Miller School of Medicine, Miami, FL, 33136, USA

    Richard J. Cote M.D., F.R.C.Path., F.C.A.P. & Ram H. Datar M.Phil., Ph.D.

Authors
  1. Zheng Ao Ph.D.
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  2. Richard J. Cote M.D., F.R.C.Path., F.C.A.P.
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  3. Ram H. Datar M.Phil., Ph.D.
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Corresponding author

Correspondence to Ram H. Datar M.Phil., Ph.D. .

Editor information

Editors and Affiliations

  1. Jackson Memorial Hospital, University of Miami, Miami, Florida, USA

    Richard J. Cote

  2. University of Miami, Miami, Florida, USA

    Ram H. Datar

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Ao, Z., Cote, R.J., Datar, R.H. (2016). Affinity-Based Enrichment of Circulating Tumor Cells. In: Cote, R., Datar, R. (eds) Circulating Tumor Cells. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3363-1_2

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  • DOI: https://doi.org/10.1007/978-1-4939-3363-1_2

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-3361-7

  • Online ISBN: 978-1-4939-3363-1

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