Abstract
The quantification of circulating tumor cells (CTCs) has been considered a potentially powerful tool in cancer diagnosis and prognosis, as CTCs have been shown to appear very early in cancer development. Great efforts have been made to develop methods that were less invasive and more sensitive to detect CTCs earlier. There is growing evidence that CTC clusters have greater metastatic potential than single CTCs. Therefore, the detection of CTC clusters is also important. This chapter is aimed to introduce a noninvasive technique for CTCs detection named in vivo flow cytometry (IVFC), which has been demonstrated to be capable of monitoring CTCs dynamics continuously. Furthermore, IVFC could be helpful for CTC cluster enumeration.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Crnic I, Christofori G (2004) Novel technologies and recent advances in metastasis research. Int J Dev Biol 48(5–6):573–581
Massagué J, Obenauf AC (2016) Metastatic colonization by circulating tumour cells. Nature 529(7586):298–306
Luzzi KJ, MacDonald IC, Schmidt EE, Kerkvliet N, Morris VL, Chambers AF et al (1998) Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early Micrometastases. Am J Pathol 153(3):865–873
Ashworth T (1869) A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J 14(3):146–149
Aceto N, Bardia A, Miyamoto David T, Donaldson Maria C, Wittner Ben S, Spencer Joel A et al (2014) Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158(5):1110–1122
Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT et al (2013) Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339(6119):580–584
Krebs MG, Hou J-M, Sloane R, Lancashire L, Priest L, Nonaka D et al (2012) Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches. J Thorac Oncol 7(2):306–315
Ting David T, Wittner Ben S, Ligorio M, Vincent Jordan N, Shah Ajay M, Miyamoto David T et al (2014) Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells. Cell Rep 8(6):1905–1918
Clare SE, Sener SF, Wilkens W, Goldschmidt R, Merkel D, Winchester DJ (1997) Prognostic significance of occult lymph node metastases in node-negative breast cancer. Ann Surg Oncol 4(6):447–451
Braun S, Pantel K, Müller P, Janni W, Hepp F, Kentenich CRM et al (2000) Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Engl J Med 342(8):525–533
Dirix L, Van Dam P, Vermeulen P (2005) Genomics and circulating tumor cells: promising tools for choosing and monitoring adjuvant therapy in patients with early breast cancer? Curr Opin Oncol 17(6):551–558
Hayes DF, Smerage J (2008) Is there a role for circulating tumor cells in the management of breast cancer? Clin Cancer Res 14(12):3646–3650
Gupta GP, Massagué J (2006) Cancer metastasis: building a framework. Cell 127(4):679–695
Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351(8):781–791
Vona G, Sabile A, Louha M, Sitruk V, Romana S, Schütze K 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, Béroud C, Damotte D, Capron F, Nalpas B et al (2004) Impact of cytomorphological detection of circulating tumor cells in patients with liver cancer. Hepatology 39(3):792–797
Riethdorf S, Fritsche H, Muller V, Rau T, Schindlbeck C, Rack B 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(3):920–928
Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C 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
Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L et al (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173):1235–1239
Sieuwerts AM, Kraan J, Bolt J, van der Spoel P, Elstrodt F, Schutte M et al (2009) Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells. J Natl Cancer Inst 101(1):61–66
Ozkumur E, Shah AM, Ciciliano JC, Emmink BL, Miyamoto DT, Brachtel E et al (2013) Inertial focusing for tumor antigen–dependent and –independent sorting of rare circulating tumor cells. Sci Transl Med 5(179):179ra147
Krivacic RT, Ladanyi A, Curry DN, Hsieh HB, Kuhn P, Bergsrud DE et al (2004) A rare-cell detector for cancer. Proc Natl Acad Sci U S A 101(29):10501–10504
Pachmann K, Clement JH, Schneider C-P, Willen B, Camara O, Pachmann U et al (2005) Standardized quantification of circulating peripheral tumor cells from lung and breast cancer. Clin Chem Lab Med 43(6):617–627
Cruz I, Ciudad J, Cruz JJ, Ramos M, Gómez-Alonso A, Adansa JC et al (2005) Evaluation of Multiparameter flow Cytometry for the detection of breast cancer tumor cells in blood samples. Am J Clin Pathol 123(1):66–74
Tinhofer I, Hristozova T, Stromberger C, KeilhoIz U, Budach V (2012) Monitoring of circulating tumor cells and their expression of EGFR/Phospho-EGFR during combined radiotherapy regimens in locally advanced squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 83(5):e685–e690
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):180ra148. * Copyright © 2013 American Association for the Advancement of Science
Givan A (2011) Flow Cytometry: an introduction. In: Hawley TS, Hawley RG (eds) Flow cytometry protocols methods in molecular biology. Humana Press, New York, pp 1–29
Robinson JP (2001) Comparative overview of flow and image Cytometry. In: Current protocols in cytometry. John Wiley & Sons Inc., New York
Pantel K, Brakenhoff RH, Brandt B (2008) Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 8(5):329–340
Lianidou ES, Markou A (2011) Circulating tumor cells in breast cancer: detection systems, molecular characterization, and future challenges. Clin Chem 57(9):1242–1255
Smith BM, Slade MJ, English J, Graham H, Lüchtenborg M, Sinnett HD et al (2000) Response of circulating tumor cells to systemic therapy in patients with metastatic breast cancer: comparison of quantitative polymerase chain reaction and immunocytochemical techniques. J Clin Oncol Off J Am Soc Clin Oncol 18(7):1432–1439
Yang M-J, Chiu H-H, Wang H-M, Yen L-C, Tsao D-A, Hsiao C-P et al (2010) Enhancing detection of circulating tumor cells with activating KRAS oncogene in patients with colorectal cancer by weighted chemiluminescent membrane array method. Ann Surg Oncol 17(2):624–633
O’Flaherty JD, Gray S, Richard D, Fennell D, O’Leary JJ, Blackhall FH et al (2012) Circulating tumour cells, their role in metastasis and their clinical utility in lung cancer. Lung Cancer 76(1):19–25
Miyamoto DT, Zheng Y, Wittner BS, Lee RJ, Zhu H, Broderick KT et al (2015) RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science 349(6254):1351–1356
Novak J, Georgakoudi I, Wei X, Prossin A, Lin CP (2004) In vivo flow cytometer for real-time detection and quantification of circulating cells. Opt Lett 29(1):77
Georgakoudi I, Solban N, Novak J, Rice WL, Wei X, Hasan T et al (2004) In vivo flow cytometry. Cancer Res 64(15):5044–5047. %* ©2004 American Association for Cancer Research
Galanzha EI, Shashkov EV, Spring PM, Suen JY, Zharov VP (2009) In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow Cytometry with a diode laser. Cancer Res 69(20):7926–7934
Galanzha EI, Kim J-W, Zharov VP (2009) Nanotechnology-based molecular photoacoustic and photothermal flow cytometry platform for in-vivodetection and killing of circulating cancer stem cells. J Biophotonics 2(12):725–735
Xu M, Wang LV (2006) Photoacoustic imaging in biomedicine. Rev Sci Instrum 77(4):041101
Zeidman I, Buss JM (1952) Transpulmonary passage of tumor cell emboli. Cancer Res 12(10):731–733
Cho EH, Wendel M, Luttgen M, Yoshioka C, Marrinucci D, Lazar D et al (2012) Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors. Phys Biol 9(1):016001
Fidler IJ (1973) The relationship of embolic homogeneity, number, size and viability to the incidence of experimental metastasis. Eur J Cancer 9(3):223–227
Molnar B, Ladanyi A, Tanko L, Sréter L, Tulassay Z (2001) Circulating tumor cell clusters in the peripheral blood of colorectal cancer patients. Clin Cancer Res 7(12):4080–4085
Stott SL, Hsu C-H, Tsukrov DI, Yu M, Miyamoto DT, Waltman BA et al (2010) Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc Natl Acad Sci 107(43):18392–18397
Hou JM, Krebs MG, Lancashire L, Sloane R, Backen A, Swain RK 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(5):525–532
Sarioglu AF, Aceto N, Kojic N, Donaldson MC, Zeinali M, Hamza B et al (2015) A microfluidic device for label-free, physical capture of circulating tumor cell clusters. Nat Methods 12(7):685–691
Li Y, Tang Z, Ye S, Liu B, Liu Y, Chen J et al Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray. J Cancer Res Clin Oncol 129(1):43–51
Acknowledgments
This work was supported by the grants of the National Major Scientific Research Program of China (Grant Nos. 2011CB910404 and 2012CB966801), the National Nature Science Foundation of China (Grant Nos. 61227017 and 81272818), and the National Science Fund for Distinguished Young Scholars (Grant No. 61425006).
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Science+Business Media LLC
About this protocol
Cite this protocol
Wei, X., Zhou, J., Zhu, X., Yang, X., Yang, P., Wang, Q. (2017). A Noninvasive and Real-Time Method for Circulating Tumor Cell Detection by In Vivo Flow Cytometry. In: M. Magbanua, M., W. Park, J. (eds) Circulating Tumor Cells. Methods in Molecular Biology, vol 1634. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7144-2_21
Download citation
DOI: https://doi.org/10.1007/978-1-4939-7144-2_21
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-7143-5
Online ISBN: 978-1-4939-7144-2
eBook Packages: Springer Protocols