Preview

Proceedings of the National Academy of Sciences of Belarus, Biological Series

Advanced search

Circulating tumor cells and circulating cancer stem cells and their detection by the method of flow cytometry

https://doi.org/10.29235/1029-8940-2021-66-3-370-384

Abstract

This review describes the circulating cancer stem cells (CCSCs) and circulating tumor cells (CTCs). CCSCs are one of the main initiators of recurrent cancer and thus make them an important target for the development of new treatment methods. CTCs are relatively new biomarkers for the early diagnosis of metastasis. CTCs provide doctors with valuable information about each stages of cancer treatments: diagnostic of early-stage disease, early detection of recurrent cancer, the efficiency of chemotherapy, and makes it possible to select an individual sensitive drug.

The most informative and frequently used markers for the detection of CSCs and CSCs were described. The mechanism of two models of tumor formation is considered: clonal and hierarchical. The known mechanisms of epithelial-mesenchymal transition of tumor cells are described. The most widely used specific cell surface markers for the detection and isolation of CTCs and CCSCs are described. The efficiency of a sensitive high-precision method of multicolor flow cytometry using specific fluorescent dye-labeled monoclonal antibodies for the detection of CCSCs and CTCs in the blood of cancer patients is analyzed. Detection of CTCs and CCSCs provides important information for the early diagnosis of metastasis and open a possibility to personalized treatment, and to monitoring of all stages cancers.

About the Authors

T. A. Pozniak
Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus
Belarus

Tatyana A. Pozniak - Ph. D. (Biol.), Senior Researcher. Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus.

27, Akademicheskaya Str., 220072, Minsk.



A. Y. Hancharou
Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus
Belarus

Andrei E. Hancharou - Ph. D. (Med.), Associate Professor, Director, Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus.

27, Akademicheskaya Str., 220072, Minsk.



V. M. Abashkin
Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus
Belarus

Viktar М. Abashkin - Junior Researcher, Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus.

27, Akademicheskaya Str., 220072, Minsk.



A. I. Stanovaya
Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus
Belarus

Alesia I. Stanovaya - Junior Researcher, Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus.

27, Akademicheskaya Str., 220072, Minsk.



A. V. Prokhorov
Belarusian State Medical University
Belarus

Alexander V. Prokhorov - D. Sc. (Med.), Professor, Head of the Department, Belarusian State Medical University.

83, Dzerzhinski Ave., 220116, Minsk.



D. G. Shcharbin
Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus
Belarus

Dzmitry G. Shcharbin - D. Sc. (Biol.), Associate Professor, Head of the Laboratory, Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus.

27, Akademicheskaya Str., 220072, Minsk.



References

1. Cancer (oncological diseases). Zdrav. Expert. Available at: http://zdrav.expert/index.php/Ctat'ya:Rak_(onkologicheckiye_zabolevaniya). (accessed 14.03.2021).

2. Kopetz S., Guthrie K. A., Morris V. K., Lenz H.-J., Magliocco A. M., Maru D. [et al.]. Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG 1406). Journal of Clinical Oncology, 2017, vol. 35, no. 4, pp. 285-294. htpps://doi.org/10.1200/JCO.20.01994

3. Antoniou A., Hebrant A., Dom G., Dumont J., Maenhaunt C. Cancer stem cells, a fuzzy evolving concept: a cell population or a cell property? Cell Cycle, 2013, vol. 12, no. 24, pp. 3743-3748. htpps://doi.org/10.4161/cc.27305

4. Bomken S., Fiser K., Heidenreich O., Vormoor J. Understanding the cancer stem cell. British Journal of Cancer, 2010, vol. 103, no. 4, pp. 439-445. https://doi.org/10.1038/sj.bjc.6605821

5. Bonnet D., Dick J. E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Medicine, 1997, vol. 3, no. 7, pp. 730-737. htpps://doi.org/10.1038/nm.0797-730

6. Eun K., Ham S. W., Kim H. Cancer stem cell heterogeneity: origin and new perspectives on CSC targeting. BMB Reports, 2017, vol. 50, no. 3, pp. 117-125. htpps://doi.org/10.5483/bmbrep.2017.50.3.222

7. Lang F., Wojcik B., Rieger M. A. Stem cell hierarchy and clonal evolution in acute lymphoblastic leukemia. Stem Cells International, 2015, vol. 2015, pp. 1-13. htpps://doi.org/10.1155/2015/137164

8. Visvader J. E., Lindeman G. J. Cancer stem cells: current status and evolving complexities. Cell Stem Cell, 2012, vol. 10, no. 6, pp. 717-728. htpps://doi.org/10.1016/j.stem.2012.05.007

9. Mani S. A. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 2008, vol. 133, pp. 704-715. htpps://doi.org/10.1016/j.cell.2008.03.027

10. Hollier B. G., Evans K., Mani S. A. The epithelial-to-mesenchymal transition and cancer stem cells: a coalition against cancer therapies. Journal of Mammary Gland Biology and Neoplasia, 2009, vol. 14, no. 1, pp. 29-43. htpps://doi.org/10.1007/s10911-009-9110-3

11. Kim Ya. S., Kaidina A. M., Chang Yu. Kh., Yarygin K. N., Lupatov A. Yu. Molecular markers of cancer stem cells verified in vivo. Biomeditsinskaya khimiya [Biomedical chemistry], 2016, vol. 62, no. 3, pp. 228-238 (in Russian).

12. Sun H., Wang S., Yan S., Zhang Yu., Nelson P., Jia H., Qin L., Dong Q. Therapeutic strategies targeting cancer stem cells and their microenvironment. Frontiers in Oncology, 2019, vol. 9, no. 9, p. 1104. htpps://doi.org/10.3389/fonc.2019.01104

13. Fillmore C. M., Kuperwasser C. Human breast cancer cell lines contain stem-like cells that selfrenew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Research, 2008, vol. 10, no. 2, art. R25. htpps://doi.org/10.1186/bcr1982

14. Ginestier C., Hur M., Charafe-Jauffret E., Birnbaum D., Wicha M., Dontu G. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell, 2007, vol. 1, no. 5, pp. 555567. htpps://doi.org/10.1016/j.stem.2007.08.014

15. Begicevic R. R., Falasca M. ABC transporters in cancer stem cells: beyond chemoresistance. International Journal of Molecular Sciences, 2017, vol. 18, p. 2362. htpps://doi.org/10.3390/ijms18112362

16. Hanahan D., Weinberg R. A. Hallmarks of cancer: the next generation. Cell, 2011, vol. 144, no. 5, pp. 646-674. htpps://doi.org/10.1016/j.cell.2011.02.013

17. Ksiqzkiewicz M., Markiewicz A., Zaczek A. J. Epithelial-mesenchymal transition: a hallmark in metastasis formation linking circulating tumor cells and cancer stem cells. Pathobiology, 2012, vol. 79, no. 4, pp. 195-208. htpps://doi.org/10.1159/000337106

18. Bonnomet A., Brysse A., Tachsidis A., Waltham M., Thompson E., Polette M., Gilles C. Epithelial-to-mesenchymal transitions and circulating tumor cells. Journal of Mammary Gland Biology and Neoplasia, 2010, vol. 15, no. 2, pp. 261-273. htpps://doi.org/10.1007/s10911-010-9174-0

19. Kalluri R. EMT: when epithelial cells decide to become mesenchymal-like cells. Journal of Clinical Investigation, 2009, vol. 119, no. 6, pp. 1417-1419. htpps://doi.org/10.1172/jci39675

20. Kalluri R., Weinberg R. A. The basics of epithelial-mesenchymal transition. Journal of Clinical Investigation, 2009, vol. 119, no. 6, pp. 1420-1428. htpps://doi.org/10.1172/jci39104

21. Chaffer C. L., Thompson E. W., Williams E. D. Mesenchymal to epithelial transition in development and disease. Cells Tissues Organs, 2007, vol. 185, no. 1-3, pp. 7-19. htpps://doi.org/10.1159/000101298

22. Chao Y. L., Shepard C. R., Wells A. Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Molecular Cancer, 2010, vol. 9, art. 179. htpps://doi.org/10.1186/1476-4598-9-179

23. Klymkowsky M. W., Savagner P. Epithelialmesenchymal transition: a cancer researcher's conceptual friend and foe. American Journal of Pathology, 2009, vol. 174, no. 5, pp. 1588-1593. htpps://doi.org/10.2353/ajpath.2009.080545

24. Tsuji T., Ibaragi S., Hu G. F. Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Research, 2009, vol. 69, no. 18, pp. 7135-7139. htpps://doi.org/10.1158/0008-5472.can-09-1618

25. Hall C., Valad L., Lucci A. Circulating tumor cells in breast cancer patients. Critical Rewievs in Oncogenesis, 2016, vol. 21, no. 1-2, pp. 125-139. htpps://doi.org/10.1615/critrevoncog.2016016120

26. Zubtsov D. A., Zubtsova Zh. I., Lavrov A. V., Legchenko E. V., Aladinskii V. A., Poteryakhina A. V., Gol'dshtein D. V. Circulating tumor cells (CTCs) in breast cancer: prognostic significance and methods for isolation. Trudy MFTI. Trudy Moskovskogo fiziko-tekhnicheskogo instituta (natsional'nogo issledovatel'skogo universiteta) [Proceedings of MIPT. Proceedings of the Moscow Institute of Physics and Technology (National Research University)], 2012, vol. 4, no. 3, pp. 18-26 (in Russian).

27. Scher H. I. Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncology, 2009, vol. 10, no. 3, pp. 233-239. htpps://doi.org/10.1016/s1470-2045(08)70340-1

28. Bidard F. C., Proudhon C., Pierga J. Y. Circulating tumor cells in breast cancer. Molecular Oncoogy, 2016, vol. 10, no. 3, pp. 418-430. htpps://doi.org/10.1016/j.molonc.2016.01.001

29. Luzzi K., MacDonald I., Schmidt E., Morris V., Chambers A. Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. American Journal of Pathology, 1998, vol. 153, no. 3, pp. 865-873. htpps://doi.org/10.1016/s0002-9440(10)65628-3

30. Berezovskaya O., Schimmer A. D., Glinskii A. B., Pinilla C., Hoffman R. M., Reed J. C., Glinsky G. V. Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells. Cancer Research, 2005, vol. 65, no. 6, pp. 2378-2386. htpps://doi.org/10.1158/0008-5472.can-04-2649

31. Gray J. W. Evidence emerges for early metastasis and parallel evolution of primary and metastatic tumors. Cancer Cell, 2003, vol. 4, no. 6, pp. 4-6. htpps://doi.org/10.1016/s1535-6108(03)00167-3

32. Michaelson J. S., Cheongsiatmoy J. A., Dewey F., Silverstein M. J., Sgroi D., Smith B., Tanabe K. K. Spread of human cancer cells occurs with probabilities indicative of a nongenetic mechanism. British Journal of Cancer, 2005, vol. 93, no. 11, pp. 1244-1249. htpps://doi.org/10.1038/sj.bjc.6602848

33. Fehm T., Solomayer E. F., Meng S., Tucker T., Lane N., Wang J., Gebauer G. Methods for isolating circulating epithelial cells and criteria for their classification as carcinoma cells. Cytotherapy, 2005, vol. 7, no. 2, pp. 171-185. htpps://doi.org/10.1080/14653240510027082

34. Man Y., Wang Q., Kemmner W. Currently Used Markers for CTC Isolation - Advantages, Limitations and Impact on Cancer Prognosis. Journal of Clinic and Experimental Pathology, 2011, vol. 1, no. 1, art. 102. https://doi.org/10.4172/2161-0681.1000102

35. Riethdorf S., Fritsche H., Muller V., Rau T., Schindlbeck C., Rack B. [et al.]. Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clinical Cancer Research, 2007, vol. 13, no. 3, pp. 920-928. htpps://doi.org/10.1158/1078-0432.ccr-06-1695

36. Maestro L., Sastre J., Rafael S., Veganzones S., Vidaurreta M., Martm M. [et al.]. Circulating tumor cells in solid tumor in metastatic and localized stages. Anticancer Research, 2009, vol. 29, no. 11, pp. 4839-4843. htpps://pubmed.ncbi.nlm.nih.gov/20032444/

37. Tol J., Koopman M. C., Miller M. C., Tibbe A., Cats A., Creemers G. J. M., Vos A. H., Nagtegaal I. D., Terstappen L. W. M. M., Punt C. J. A. Circulating tumour cells early predict progression-free and overall survival in advanced colorectal cancer patients treated with chemotherapy and targeted agents. Annals of Oncology, 2010, vol. 21, no. 5, pp. 1006-1012. htpps://doi.org/10.1093/annonc/mdp463

38. Fischer K., Durrans A., Lee S., Sheng J., Li F., Wong S. [et al.]. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature, 2015, vol. 527, no. 7579, pp. 472-476. htpps://doi.org/10.1038/nature15748

39. Beltran H., Jendrisak A., Landers M., Mosquera J., Kossa M., Louw J. [et al.]. The initial detection and partial characterization of circulating tumor cells in neuroendocrine prostate cancer. Clinical Cancer Research, 2016, vol. 22, no. 6, pp. 1510-1519. htpps://doi.org/10.1158/1078-0432.ccr-15-0137

40. Lianidou E. S., Markou A. Circulating tumor cells as emerging tumor biomarkers in breast cancer. Clinical Chemistry and Laboratory Medicine, 2011, vol. 49, no. 10, pp. 1579-1590. htpps://doi.org/10.1515/cclm.2011.628

41. Eslami S. Z., Cortes-Hernandez L. E., Alix-Panabieres C. Circulating tumor cells: moving forward into clinical applications. Precision Cancer Medicine, 2020, vol. 3, no. 4, pp. 781-791. htpps://doi.org/10.1016/j.mam.2019.07.008

42. Sieuwerts A. M., Kraan J., Bolt J., van der Spoel P., Elstrodt F., Schutte M., Martens J. W. M., Gratama J. W., Sleijfer S., Foekens J. A. Antiepithelial cell adhesion molecule antibodies and the detection of circulating normallike breast tumor cells. Journal of the Nature Cancer Institute, 2009, vol. 101, no. 1, pp. 61-66. htpps://doi.org/10.1093/jnci/djn419

43. Punnoose E. A., Atwal S. K., Spoerke J. M., Savage H., Pandita A., Yeh R. [et al.]. Molecular biomarker analyses using circulating tumor cells. PLoS ONE, 2010, vol. 5, no. 9, p. e12517. htpps://doi.org/10.1371/journal.pone.0012517

44. Mikolajczyk S. D., Millar L. S., Tsinberg P., Coutts S. M., Zomorrodi M., Pham T., Bischoff F. Z., Pircher T. J. Detection of EpCAM negative and cytokeratin-negative circulating tumor cells in peripheral blood. Journal of Oncology, 2011, vol. 2011, pp. 252-361. htpps://doi.org/10.1155/2011/252361

45. Vila A., Abal M., Muinelo-Romay L., Rodriguez-Abreu C., Rivas J., Lopez-Lopez R., Costa C. EGFR-based immunoisolation as a recovery target for Low-EpCAM CTC subpopulation. PLoS ONE, 2016, vol. 11, no. 10, p. e0163705. htpps://doi.org/10.1371/journal.pone.0163705

46. Winter S. A., Stephenson S. A., Subramaniam S. K., Paleri V., Ha K., Marnane C., Krishnan S., Rees G. Long-term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma. BMC Cancer, 2009, vol. 9, no. 1, art. 424. htpps://doi.org/10.1186/1471-2407-9-424

47. Yu X. M., Yi-Chen Wu, Xiang Liu, Xian-Cong Huang, Xiu-Xiu Hou, Jiu-Li Wang, Xiang-Liu Cheng, Wei-Min Mao, Zhi-Qiang Ling. Cell-free RNA content in peripheral blood as potential biomarkers for detecting circulating tumor cells in non-small cell lung carcinoma. International Journal of Molecular Sciences, 2016, vol. 17, no. 11, p. 1845. https://doi.org/10.3390/ijms17111845

48. Pestrin M., Bessi S., Galardi F., Truglia M., Biggeri A., Biagioni C., Cappadona S., Biganzoli L., Giannini A., Di Leo A. Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients. Breast Cancer Research and Treatment, 2009, vol. 118, no. 3, pp. 523-530. htpps://doi.org/10.1007/s10549-009-0461-7

49. Chen W., Zhang J., Huang L., Chen L., Zhou Y., Tang D., Xie Y., Wang H., Huang C. Detection of HER2-positive circulating tumor cells using the LiquidBiopsy System in breast cancer. Clinical Breast Cancer, 2019, vol. 19, no. 1, pp. 239-246. htpps://doi.org/10.1016/j.clbc.2018.10.009

50. Dotan E., Alpaugh K., Ruth K., Negin B. P., Denlinger C. S., Hall M. J., Astsaturov I., McAleer, C., Fittipaldi P., Thrash-Bingham C., Meropol N., Cohen S. J. Pancreas, 2016, vol. 45, no. 8, pp. 1131-1135. htpps://doi.org/10.1097/mpa.0000000000000619

51. Cheng J.-P., Yan Y., Wang X.-Y., Lu Y.-L., Lu Y.-L., Jia J., Ren J. MUC1-positive circulating tumor cells and MUC1 protein predict chemotherapeutic efficacy in the treatment of metastatic breast cancer. Cancer Communications, 2011, vol. 30, no. 1, pp. 54-61. htpps://doi.org/10.5732/cjc.010.10239

52. Park S. Y., Choi G. S., Park J. S., Kim H. J., Ryuk J. P., Choi W. H. Influence of surgical manipulation and surgical modality on the molecular detection of circulating tumor cells from colorectal cancer. Journal of Korean Surgical Society, 2012, vol. 82, no. 6, pp. 356-364. htpps://doi.org/10.4174/jkss.2012.82.6.356

53. Baigenzhin A., Shaimardanova G., Popova N., Zhussipova B., Ismailova G. Git'culating tumour cells: molecular properties and anti-cancer treatment monitoring. Journal of Clinical Medicine of Kazakhstan, 2013, vol. 4, no. 30, pp. 9-13.

54. Paterlini-Brechot P., Benali N. L. Circulating tumor cells (CTC) detection: clinical impact and future directions. Cancer Letters, 2007, vol. 253, no. 2, pp. 180-204. htpps://doi.org/10.1016/j.canlet.2006.12.014

55. Sastre J., Maestro M. L., Gomez-Espana A., Rivera F., Valladares M., Massuti B. [et al.]. Circulating tumor cell count is a prognostic factor in metastatic colorectal cancer patients receiving first-line chemotherapy plus bevacizumab: a Spanish Cooperative Group for the Treatment of Digestive Tumors study. Oncologist, 2012, vol. 17, no. 7, pp. 947-955. https://doi.org/10.1634/theoncologist.2012-0048

56. Paoletti C., Hayes D. F. Circulating tumor cells. Novel Biomarkers in the Continuum of Breast Cancer. Vol. 882. Cham, 2016, pp. 235-258.

57. Gwatkin R. B. L. Practical flow cytometry, by H. M. Shapiro, Wiley-Liss, New York, 3rd ed., 1994, 542 p. Molecular Reproduction and Development, 1995, vol. 41, no. 4, p. 530. htpps://doi.org/10.1002/mrd.1080410419

58. Rajab A., Axler O., Leung J., Wozniak M., Porwit A. Ten-color 15-antibody flow cytometry panel for immunophenotyping of lymphocyte population. International Journal of Laboratory Hematology, 2017, vol. 39, suppl. 1, pp. 76-85. htpps://doi.org/10.1111/ijlh.12678

59. Tao L., Su L., Yuan C., Ma Z., Zhang L., Bo S., Niu Y., Lu S., Xiu D. Postoperative metastasis prediction based on portal vein circulating tumor cells detected by flow cytometry in periampullary or pancreatic cancer. Cancer Management and Research, 2019, vol. 11, pp. 7405-7425. https://doi.org/10.2147/cmar.s210332

60. Lu Y., Liang H., Yu T., Xie J., Chen S., Dong H. [et al.]. Isolation and characterization of living circulating tumor cells in patients by immunomagnetic negative enrichment coupled with flow cytometry. Cancer, 2015, vol. 121, no. 17, pp. 3036-3045 https://doi.org/10.1002/cncr.29444

61. Xu J., Jorgensen J. L., Wang S. A. How do we use multicolor flow cytometry to detect minimal residual disease in acute myeloid leukemia? Clinics in Laboratory Medicine, 2017, vol. 37, no. 4, pp. 787-802. https://doi.org/10.1016/j.cll.2017.07.004

62. Goncharov A. E., Timokhina O. B. Method for determining circulating tumor cells. Patent BY 23371, 2021 (in Russian).


Review

Views: 1144


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1029-8940 (Print)
ISSN 2524-230X (Online)