Copyright: © 2025 by the authors. Licensee: Pirogov University.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (CC BY).

ORIGINAL RESEARCH

Characteristics of the metastasis-associated circulating cells: features of side scatter parameters

About authors

1 Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia

2 Siberian State Medical University, Tomsk, Russia

3 Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia

Correspondence should be addressed: Angelina V. Buzenkova
Kooperativny per., 5, Tomsk, 634009, Russia; ur.liam@va_avoknezub

About paper

Funding: the study was supported by the RSF grant No. № 23-15-00135.

Author contribution: Buzenkova AV — literature review, data analysis, acquisition and statistical processing of the results, manuscript writing; Grigoryeva ES — flow cytometry, data analysis, interpretation of the results, manuscript writing; Alifanov VV — flow cytometry, manuscript editing; Tashireva LA, Savelieva OE — discussion, manuscript editing; Pudova ES — flow cytometry; Zavyalova MV — manuscript editing; Cherdyntseva NV — study planning and design, discussion; Perelmuter VM — study planning and management, interpretation of the results, manuscript writing.

Compliance with ethical standards: the study was approved by the Ethics Committee of the Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences (protocol No. 8 dated 17 June 2016) and conducted in accordance with Federal Laws of the Russian Federation (No. 152, 323, etc.), the Declaration of Helsinki (1964) and all later amendments and additions that regulate scientific research involving human biomaterial. All subjects submitted the informed consent to participation in the study.

Received: 2025-03-11 Accepted: 2025-03-26 Published online: 2025-04-18
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  1. Riethdorf S, Fritsche H, Müller V, Rau T, Schindlbeck C, Rack B, et al. Detection of circulating tumor cells in peripheral blood of patients with metastatic BC: A validation study of the CellSearch system. Clin Cancer Res. 2007; 13 (3): 920–8. DOI: 10.1158/1078-0432.CCR-06-1695. PMID: 17289886.
  2. Vidlarova M, Rehulkova A, Stejskal P, Prokopova A, Slavik H, Hajduch M, et al. Recent Advances in Methods for Circulating Tumor Cell Detection. Int J Mol Sci. 2023; 24 (4): 3902. DOI: 10.3390/ijms24043902. PMID: 36835311.
  3. Fabisiewicz A, Szostakowska-Rodzos M, Zaczek AJ, Grzybowska EA. Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value. Int J Mol Sci. 2020; 21 (5): 1671. DOI: 10.3390/ijms21051671. PMID: 32121386.
  4. Tashireva LA, Savelieva OE, Grigoryeva ES, Nikitin YV, Denisov EV, et al. Heterogeneous Manifestations of Epithelial-Mesenchymal Plasticity of Circulating Tumor Cells in Breast Cancer Patients. Int J Mol Sci. 2021; 22 (5): 2504. DOI: 10.3390/ijms22052504. PMID: 33801519.
  5. Savelieva OE, Tashireva LA, Kaigorodova EV, Buzenkova AV, Mukhamedzhanov RKh, Grigoryeva ES, et al. Heterogeneity of Stemlike Circulating Tumor Cells in Invasive Breast Cancer. Int J Mol Sci. 2020; 21 (8): 2780. DOI: 10.3390/ijms21082780. PMID: 32316333.
  6. Xu W, Yuan F. Detection of Circulating Tumor Cells in the Prognostic Significance of Patients with Breast Cancer: A Retrospective Study. J Clin Lab Anal. 2025; 39 (1): e25126. DOI: 10.1002/jcla.25126. PMID: 39692703.
  7. Perelmuter VM, Grigoryeva ES, Savelieva OE, Alifanov VV, Andruhova ES, Zavyalova MV, et al. EpCAM–CD24+ circulating cells associated with poor prognosis in breast cancer patients. Sci Rep. 2024; 14 (1): 12245. DOI: 10.1038/s41598-024-61516-2. EDN: XZHVTO.
  8. Chabot-Richards DS, George TI. White blood cell counts. Clin Lab Med. 2015; 35 (1): 11–24. DOI: 10.1016/j.cll.2014.10.007. PMID: 25676369.
  9. Wu T, Tan JHL, Sin WX, Luah YH, Tan SY, Goh M, et al. Cell granularity reflects immune cell function and enables selection of lymphocytes with superior attributes for immunotherapy. Adv Sci. 2023; 10 (28): e2302175. DOI: 10.1002/advs.202302175. PMID: 37544893.
  10. Watson D, Hagen N, Diver J, Marchand P, Chachisvilis M. Elastic light scattering from single cells: orientational dynamics in optical trap. Biophys J. 2004; 87 (2): 1298–306. DOI: 10.1529/biophysj.104.042135. PMID: 15298932.
  11. Grigoryeva ES, Tashireva LA, Alifanov VV, Savelieva OE, Vtorushin SV, Zavyalova MV, et al. Molecular subtype conversion in CTCs as indicator of treatment adequacy associated with metastasis-free survival in breast cancer. Sci Rep. 2022; 12 (1): 20949. DOI: 10.1038/s41598-022-25609-0. PMID: 36470982.
  12. Sterzynska K, Kempisty B, Zawierucha P, Zabel M. Analysis of the specificity and selectivity of anti-EpCAM antibodies in breast cancer cell lines. Folia Histochem Cytobiol. 2012; 50 (4): 534–41. DOI: 10.5603/17845. PMID: 23264216.
  13. Gorges TM, Tinhofer I, Drosch M, Röse L, Zollner TM, Krahn T, et al. Circulating tumor cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC cancer. 2012; 50 (4): 534–41. DOI: 10.1186/1471-2407-12-178. PMID: 22591372.
  14. Königsberg R, Obermayr E, Bises G, Pfeiler G, Gneist M, Wrba F, et al. Detection of EpCAM positive and negative circulating tumor cells in metastatic breast cancer patients. Acta Oncol. 2011; 50 (5): 700–10. DOI: 10.3109/0284186X.2010.549151. PMID: 21261508.
  15. Driemel C, Kremling H, Schumacher S, Will D, Wolters J, Lindenlauf N, et al. Context-dependent adaption of EpCAM expression in early systemic esophageal cancer. Oncogene. 2014; 33 (41): 4904–15. DOI: 10.1038/onc.2013.441. PMID: 24141784.
  16. Perelmuter VM, Manskikh VN. Prenisha as the missing link of the metastatic niche concept explaining selective metastasis of malignant tumors and the pattern of metastatic disease. Biochemistry (Mosc). 2012; 77 (1): 111-8. DOI: 10.1134/S0006297912010142. PMID: 22339641.
  17. Fox JM, Chamberlain G, Ashton BA. Recent advances into the understanding of mesenchymal stem cell trafficking. Br J Haematol. 2007; 137 (6): 491–502. DOI: 10.1111/j.1365-2141.2007.06610. x. PMID: 17539772.
  18. Huang Y, Chanou A, Kranz G, Pan M, Kohlbauer V, Ettinger A, et al. Membrane-associated epithelial cell adhesion molecule is slowly cleaved by γ-secretase prior to efficient proteasomal degradation of its intracellular domain. JBC. 2019; 294 (9): 3051– 64. DOI: 10.1074/jbc.RA118.005874. PMID: 30598504.
  19. Schreier S & Triampo W. The blood circulating rare cell population. What is it and what is it good for? Cells. 2020; 9 (4): 790. DOI: 10.3390/cells9040790. PMID: 32218149.
  20. Holtorf S, Boyle J, Morris R. Evidence for EpCAM and cytokeratin expressing epithelial cells in normal human and murine blood and bone marrow. JoVE. 2023; (194): 10.3791/65118. DOI: 10.3791/65118. PMCID: PMC10653199.
  21. Kassmer SH & Krause DS. Detection of bone marrow–derived lung epithelial cells. Exp Hematol. 2010; 38 (7): 564–73. DOI: 10.1016/j.exphem.2010.04.011. PMID: 20447442.
  22. Van Arnam JS, Herzog E, Grove J, Bruscia E, Ziegler E, Swenson S. Engraftment of bone marrow-derived epithelial cells. Stem Cell Rev. 2005; 1 (1): 21–7. DOI: 10.1385/SCR:1:1:021. PMID: 17132871.
  23. Borue X, Lee S, Grove J, Herzog EL, Harris R, Diflo T, et al. Bone marrow-derived cells contribute to epithelial engraftment during wound healing. Am J Pathol. 2004; 165 (5): 1767–72. DOI: 10.1016/S0002-9440(10)63431-1. PMID: 15509544.
  24. Solovjov DA, Pluskota E, Plow EF. Distinct roles for the alpha and beta subunits in the functions of integrin alphaMbeta2. JBC. 2005; 280 (2): 1336–45. DOI: 10.1074/jbc.M406968200. PMID: 15485828.
  25. Han C, Jin J, Xu S, Liu H, Li N, Cao X. Integrin CD11b negatively regulates TLR-triggered inflammatory responses by activating Syk and promoting degradation of MyD88 and TRIF via Cbl-b. Nat Immunol. 2010; 11 (8): 734–42. DOI: 10.1038/ni.1908. PMID: 20639876.
  26. Schmid MC, Khan SQ, Kaneda MM, Pathria P, Shepard R, Louis TL, et al. Integrin CD11b activation drives anti-tumor innate immunity. Nat Commun. 2018; 9 (1): 5379. DOI: 10.1038/s41467-018-07387-4. PMID: 30568188. 28.
  27. Lambert C, Preijers FW, Yanikkaya Demirel G, Sack U. Monocytes and macrophages in flow: an ESCCA initiative on advanced analyses of monocyte lineage using flow cytometry. Cytometry B Clin Cytom. 2017; 92 (3): 180–8. DOI: 10.1002/cyto.b.21280. PMID: 26332381.
  28. Johansson J, Tabor V, Wikell A, Jalkanen S, Fuxe J. TGF-β1Induced Epithelial-Mesenchymal Transition Promotes Monocyte/Macrophage Properties in Breast Cancer Cells. Front Oncol. 2015; 5: 3. DOI: 10.3389/fonc.2015.00003. PMID: 25674539.