JOURNAL DESCRIPTION
The Medical Radiology and Radiation Safety journal ISSN 1024-6177 was founded in January 1956 (before December 30, 1993 it was entitled Medical Radiology, ISSN 0025-8334). In 2018, the journal received Online ISSN: 2618-9615 and was registered as an electronic online publication in Roskomnadzor on March 29, 2018. It publishes original research articles which cover questions of radiobiology, radiation medicine, radiation safety, radiation therapy, nuclear medicine and scientific reviews. In general the journal has more than 30 headings and it is of interest for specialists working in thefields of medicine¸ radiation biology, epidemiology, medical physics and technology. Since July 01, 2008 the journal has been published by State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. The founder from 1956 to the present time is the Ministry of Health of the Russian Federation, and from 2008 to the present time is the Federal Medical Biological Agency.
Members of the editorial board are scientists specializing in the field of radiation biology and medicine, radiation protection, radiation epidemiology, radiation oncology, radiation diagnostics and therapy, nuclear medicine and medical physics. The editorial board consists of academicians (members of the Russian Academy of Science (RAS)), the full member of Academy of Medical Sciences of the Republic of Armenia, corresponding members of the RAS, Doctors of Medicine, professor, candidates and doctors of biological, physical mathematics and engineering sciences. The editorial board is constantly replenished by experts who work in the CIS and foreign countries.
Six issues of the journal are published per year, the volume is 13.5 conventional printed sheets, 88 printer’s sheets, 1.000 copies. The journal has an identical full-text electronic version, which, simultaneously with the printed version and color drawings, is posted on the sites of the Scientific Electronic Library (SEL) and the journal's website. The journal is distributed through the Rospechat Agency under the contract № 7407 of June 16, 2006, through individual buyers and commercial structures. The publication of articles is free.
The journal is included in the List of Russian Reviewed Scientific Journals of the Higher Attestation Commission. Since 2008 the journal has been available on the Internet and indexed in the RISC database which is placed on Web of Science. Since February 2nd, 2018, the journal "Medical Radiology and Radiation Safety" has been indexed in the SCOPUS abstract and citation database.
Brief electronic versions of the Journal have been publicly available since 2005 on the website of the Medical Radiology and Radiation Safety Journal: http://www.medradiol.ru. Since 2011, all issues of the journal as a whole are publicly available, and since 2016 - full-text versions of scientific articles. Since 2005, subscribers can purchase full versions of other articles of any issue only through the National Electronic Library. The editor of the Medical Radiology and Radiation Safety Journal in accordance with the National Electronic Library agreement has been providing the Library with all its production since 2005 until now.
The main working language of the journal is Russian, an additional language is English, which is used to write titles of articles, information about authors, annotations, key words, a list of literature.
Since 2017 the journal Medical Radiology and Radiation Safety has switched to digital identification of publications, assigning to each article the identifier of the digital object (DOI), which greatly accelerated the search for the location of the article on the Internet. In future it is planned to publish the English-language version of the journal Medical Radiology and Radiation Safety for its development. In order to obtain information about the publication activity of the journal in March 2015, a counter of readers' references to the materials posted on the site from 2005 to the present which is placed on the journal's website. During 2015 - 2016 years on average there were no more than 100-170 handlings per day. Publication of a number of articles, as well as electronic versions of profile monographs and collections in the public domain, dramatically increased the number of handlings to the journal's website to 500 - 800 per day, and the total number of visits to the site at the end of 2017 was more than 230.000.
The two-year impact factor of RISC, according to data for 2017, was 0.439, taking into account citation from all sources - 0.570, and the five-year impact factor of RISC - 0.352.
Medical Radiology and Radiation Safety. 2025. Vol. 70. № 2
DOI:10.33266/1024-6177-2025-70-2-9-15
P.A. Malakhov1, M.V. Pustovalova1, A.V. Aleksandrova1, E.G. Kontareva1,
A.V. Smirnova1, Z. Nofal1, A.N. Osipov1, 2, S.V. Leonov1
Repetitive Confined Migration Leads to an Increase in Clonogenic Activity and Chemoresistanse of Human Non-Small Cell Lung Cancer Cells, Regardless of Their Initial Chemo- and Radiosensitivity
1 Moscow Institute of Physics and Technology (National Research University), Dolgoprudny, Russia
2 A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia
Contact person: M.V. Pustovalova, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Purpose: Radiation therapy can treat non-small cell lung cancer (NSCLC), but its effectiveness is limited by the development of tumor radioresistance. Studies have shown that radiation can affect tumor aggressiveness, either reducing or increasing the invasiveness of remaining cancer cells, depending on the cell lines and radiation type. However, the effect of tumor cell migration in the confined porous space of tumor tissue on their phenotypic characteristics is not well understood. This study aimed to investigate how migration in confined spaces affects the phenotypic traits of two NSCLC isogenic cell lines with varying levels of radioresistance, invasiveness, and repopulation ability.
Material and methods: The biophysical impact on the A549 cell line and its isogenic radioresistant subline A549IR was carried out by their sequential triple migration in a limited space of membrane pores with a diameter of 8 μm in Boyden chambers, following the concentration gradient of fetal bovine serum. The ability to repopulate cell populations migrated across membranes was characterized using clonogenic analysis. We assessed markers such as Ki67 (cell cycle activity), vimentin (a cytoskeletal protein linked to migration and metastasis), and fluorescent nanosensor uptake (indicating metastasis potential) through quantitative analysis of digital images from high-content imaging of individual cells. A standard method for determining cell mass with the dye sulphorodamine B after exposure to different concentrations of cisplatin was used to assess the chemosensitivity of tumor cells before and after migration.
Results and Conclusion: The study shows that repeated migration through an 8 μm pore, which simulates conditions cancer cells experience during metastasis, deforms the nuclei of non-small cell lung cancer (NSCLC) cells. This deformation reduces Ki67-related chromatin reorganization and alters gene expression, notably increasing vimentin. This results in increased chemoresistance and a greater likelihood of repopulation and metastasis in these cells, regardless of their initial ability to migrate or their sensitivity to chemotherapy and radiation.
Keywords: non-small cell lung cancer, radioresistance, chemoresistance, confined migration, metastatic activity, endocytosis, nanosensors
For citation: Malakhov PA, Pustovalova MV, Aleksandrova AV, Kontareva EG, Smirnova AV, Nofal Z, Osipov AN, Leonov SV. Repetitive Confined Migration Leads to an Increase in Clonogenic Activity and Chemoresistanse of Human Non-Small Cell Lung Cancer Cells, Regardless of Their Initial Chemo- and Radiosensitivity. Medical Radiology and Radiation Safety. 2025;70(2):9–15. (In Russian). DOI:10.33266/1024-6177-2025-70-2-9-15
References
1. Aupérin A., Le Péchoux C., Rolland E., et al. Meta-Analysis of Concomitant Versus Sequential Radiochemotherapy in Locally Advanced Non-Small-Cell Lung Cancer. J Clin On col. 2010;28;13:2181-2190. doi: 10.1200/JCO.2009.26.2543. PMID: 20351327.
2. Friedl P., Wolf K. Tumour-Cell Invasion and Migration: Diversity and Escape Mechanisms. Nat Rev Cancer. 2003;3;5:362 374. doi:10.1038/nrc1075. PMID: 12724734.
3. Fanfone D., Wu Z., Mammi J., et al. Confined Migration Promotes Cancer Metastasis Through Resistance to Anoikis and Increased Invasiveness. Elife. 2022;11:e73150. doi:10.7554/ eLife.73150. PMID: 35256052.
4. Fujita, M., Yamada, S., & Imai, T. (2015). Irradiation induces diverse changes in invasive potential in cancer cell lines. Seminars in cancer biology, 35, 45–52. https:// doi.org/10.1016/j.semcancer.2015.09.003
5. Shieh A.C. Biomechanical Forces Shape the Tumor Microenvironment. Ann Biomed Eng. 2011;39;5:1379-1389. doi:10.1007/ s10439-011-0252-2. PMID: 21253819.
6. Pustovalova M., Alhaddad L., Smetanina N., et al. The p53 53BP1-Related Survival of A549 and H1299 Human Lung Cancer Cells after Multifractionated Radiotherapy Demonstrated Different Response to Additional Acute X-ray Exposure. Int J Mol Sci. 2020;21;9:3342. doi:10.3390/ijms21093342. PMID: 32397297.
7. Merkher Y., Kontareva E., Bogdan E., et al. Encapsulation and Adhesion of Nanoparticles as a Potential Biomarker for TNBC Cells Metastatic Propensity. Sci Rep. 2023;13;1:12289. doi:10.1038/s41598-023-33540-1. PMID: 37516753.
8. Wang M., Yi J., Gao H., et al. Radiation-Induced YAP/TEAD4 Binding Confers Non-Small Cell Lung Cancer Radioresistance Via Promoting NRP1 Transcription. Cell Death Dis. 2024;15;8:619. doi:10.1038/s41419-024-07017-6. PMID: 39187525.
9. Alhaddad L., Pustovalova M., Blokhina T., Chuprov-Netochin R., Osipov A.N., Leonov S. IR-Surviving NSCLC Cells Exhibit Different Patterns of Molecular and Cellular Reactions Relating to the Multifraction Irradiation Regimen and p53-Family Proteins Expression. Cancers (Basel). 2021;13;11:2669. doi:10.3390/cancers13112669. PMID: 34071477.
10. Gan, Z., Ding, L., Burckhardt, C. J., Lowery, J., Zaritsky, A., Sitterley, K., Mota, A., Costigliola, N., Starker, C.G., Voytas, D.F., Tytell, J., Goldman, R.D., & Danuser, G. (2016). Vimentin Intermediate Filaments Template Microtubule Networks to Enhance Persistence in Cell Polarity and Directed Migration. Cell systems, 3(3), 252–263.e8.
11. Mendez, M. G., Restle, D., & Janmey, P. A. (2014). Vimentin enhances cell elastic behavior and protects against compressive stress. Biophysical journal, 107(2), 314–323. https://doi. org/10.1016/j.bpj.2014.04.050/
12. Hu, J., Li, Y., Hao, Y., Zheng, T., Gupta, S. K., Parada, G. A., Wu, H., Lin, S., Wang, S., Zhao, X., Goldman, R. D., Cai, S., & Guo, M. (2019). High stretchability, strength, and toughness of living cells enabled by hyperelastic vimentin intermediate filaments. Proceedings of the National Academy of Sciences of the United States of America, 116(35), 17175–17180. https:// doi.org/10.1073/pnas.1903890116.
13. Xuan, B., Ghosh, D., Cheney, E. M., Clifton, E. M., & Dawson, M. R. (2018). Dysregulation in Actin Cytoskeletal Organization Drives Increased Stiffness and Migratory Persistence in Polyploidal Giant Cancer Cells. Scientific reports, 8(1), 11935. https://doi.org/10.1038/s41598-018-29817-5.
14. Esue O., Carson A.A., Tseng Y., Wirtz D. A Direct Interaction between Actin and Vimentin Filaments Mediated by the Tail Domain of Vimentin. J Biol Chem. 2006;281;41:30393-30399. doi:10.1074/jbc.M605452200. PMID: 16901892.
15. Shen Q, Hill T, Cai X, Bui L, Barakat R, Hills E, Almugaiteeb T, Babu A, Mckernan PH, Zalles M, Battiste JD, Kim YT. Physical confinement during cancer stem cell-like behavior. Cancer Lett. 2021 May 28;506:142-151. doi: 10.1016/j.canlet.2021.01.020
16. Bunn P.A. Jr. The Expanding Role of Cisplatin in the Treatment of Non-Small-Cell Lung Cancer. Semin Oncol. 1989;16;4;6:10 21. PMID: 2548280.
17. Cho K., Choi E.S., Kim J.H., Son J.W., Kim E. Numerical Learning of Deep Features from Drug-Exposed Cell Images to Calculate IC50 without Staining. Sci Rep. 2022;12;1:6610. Published 2022 Apr 22. doi:10.1038/s41598-022-10643-9. PMID: 35459284.
18. Xuan, B., Ghosh, D., Jiang, J., Shao, R., & Dawson, 19. M.R. (2020). Vimentin filaments drive migratory persistence in polyploidal cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 117(43), 26756–26765. https://doi. org/10.1073/pnas.2011912117
19. Valeriote, F. and L. van Putten, Proliferation-dependent cytotoxicity of anticancer agents: a review. Cancer research, 1975. 35(10): p. 2619-2630;
20. Stover, D.G., et al, The Role of Proliferation in Determining Response to Neoadjuvant Chemotherapy in Breast Cancer: A Gene Expression–Based Meta-Analysis. Clinical Cancer Research, 2016. 22(24): p. 6039-6050.
21. Tubiana, M. et al, The long-term prognostic significance of the thymidine labelling index in breast cancer. International journal of cancer, 1984. 33(4): p. 441−445
22. Miller, I. et al, Ki67 is a graded rather than a binary marker of proliferation versus quiescence. Cell reports, 2018. 24(5): p. 1105−1112. e5
23. Sobecki, M., et al, The cell proliferation antigen Ki-67 organises heterochromatin. elife, 2016. 5: p. e13722;
24. Mrouj, K., et al, Ki 67 regulates global gene expression and promotes sequential stages of carcinogenesis. Proceedings of the National Academy of Sciences, 2021. 118(10): p. e2026507118.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The work was supported by the Ministry of Science and Higher Education of the Russian Federation (State Assignment): “Development of local drug delivery systems for medical purposes”, number FSMG-2023-0015, agreement number No. 075-03-2024-117 dated 17.01.2024.
Contribution. Article was prepared with equal participation of the authors.
Article received: 20.12.2024. Accepted for publication: 25.01.2025.