How to Cite
Abstract
The approach to the management of cancerous neoplasms, which aims to define the effective curative strategies in each patient, defines the requirement for the elaboration and use of modelling systems that replicate the structures and the biology of human solitary tumors. Three-dimensional cultures of spheroids/tumoroids, which are multi-cell aggregates of malignized cells, can create the intercellular connections of interest, gradients of the nutrients and oxygen, and cell polarity, all of which are absent in the conventional two-dimensional single-layer system.
The present work is dedicated to a comparison study of in vitro viability and invasiveness of solid tumor cells of patients under the effect of chemopreparations and their combinations in view of evaluating the efficacy of the 3D-cell modelling system in the translational personalized medicine context.
Cell cultures of patients who were treated at the N.N. Petrov National Medicine Research Center of oncology were used as a basis for the development of 3D-cell models. N.N. Petrov NMRC in 2015-2021. Tumor tissue pieces were acquired intraoperatively: 1 - leiomyosarcoma (LMS), 1 - rhabdomyosarcoma (RMS), 1 - synovial sarcoma (SS), 2 - myxofibrosarcoma (MFS), 2 - osteogenic sarcoma (OS), 1 - skin melanoma (MC), 1 - breast cancer (BC) (n=9).
Our individual comparison of the effectiveness of in vitro chemotherapeutic agents against tumor cells of various origins cultivated in 2D and 3D model systems with real clinically relevant cases confirmed that the monolayer culture as the test system was less adequate for selecting and personalizing the treatment of malignant tumor patients: the 3D cell system proved itself in 77.7% of cases, and the monolayer culture - in 44.4% of cases. The combination of doxorubicin/iforsfamide and paclitaxel significantly suppressed the motility in the matrigel of spheroid cells, but did not affect tumor cell viability, which was seen in all but OS #921 and MK #929 cases.
The cultivation of tumor cells in form of spheroids/tumoroids allows to utilize them as more adequate pre-clinical model as individual predictive test-system, enabling the personalized selection of therapy.
References
Pauli C et al. Personalized in vitro and in vivo cancer models to guide precision medicine // Cancer Discov. 2017;7(5):462–477. doi: 10.1158/2159-8290.CD-16-1154
Kitaeva KV, Rutland CS, Rizvanov AA, Solovyeva VV. Cell Culture Based in vitro Test Systems for Anticancer Drug Screening // Front Bioeng Biotechnol. 2020;8. doi: 10.3389/fbioe.2020.00322
Han SJ, Kwon S, Kim KS. Challenges of applying multicellular tumor spheroids in preclinical phase // Cancer Cell Int. 2021;21(1). doi: 10.1186/s12935-021-01853-8
Pinto C, Estrada MF, Brito C. In Vitro and Ex Vivo Models — The Tumor Microenvironment in a Flask // Adv Exp Med Biol. 2020;1219:431–443.
Tsuruno Y, Okubo K, Fujiwara T et al. An in vitro model for determining tumor cell migration under metabolic gradients // Adv Exp Med Biol. 2018;1072:201–205.
Bhattacharya S, Calar K, De La Puente P. Mimicking tumor hypoxia and tumor-immune interactions employing three-dimensional in vitro models // J Exp Clin Cancer Res. 2020;39(1). doi: 10.1186/s13046-020-01583-1
Zanoni M, Pignatta S, Arienti C et al. Anticancer drug discovery using multicellular tumor spheroid models // Expert Opin Drug Discov. 2019;14(3):289–301. doi:10.1080/17460441.2019.1570129
Bassi G, Grimaudo MA, Panseri S, Montesi M. Advanced multi-dimensional cellular models as emerging reality to reproduce In Vitro the human body complexity // Int J Mol Sci. 2021;22(3):1–28. doi: 10.3390/ijms22031195
Kuen J, Darowski D, Kluge T, Majety M. Pancreatic cancer cell/fibroblast co-culture induces M2 like macrophages that influence therapeutic response in a 3D model // PLoS One. 2017; 12(7). doi: 10.1371/journal.pone.0182039
Liu X et al. A novel simpledrop chip for 3d spheroid formation and anti-cancer drug assay // Micromachines. 2021;12(6). doi: 10.3390/mi12060681
Freshney RI. Culture of Animal Cells. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2010.
Danilov AO et al. An improved procedure for autologous gene-modified vaccine preparation for active specific immunotherapy of disseminated solid tumors // Vopr. Onkol. 2004.
Salmon SE. Cloning of Human tumor stem cells: background and overview // Prog. Clin. Biol. Res. 1980;48:3–13.
Everitt BS, Pickles A. Statistical Aspects of the Design and Analysis of Clinical Trials. PUBLISHED BY IMPERIAL COLLEGE PRESS AND DISTRIBUTED BY WORLD SCIENTIFIC PUBLISHING CO., 2004.
Ulukaya E, Karakas D, Dimas K. Tumor chemosensitivity assays are helpful for personalized Cytotoxic treatments in cancer patients // Medicina (Kaunas). 2021;57(6). doi: 10.3390/medicina57060636
Cui X, Hartanto Y, Zhang H. Advances in multicellular spheroids formation // J R Soc Interface. 2017;14(127). doi: 10.1098/rsif.2016.0877
S. L’Espérance SL, M. Bachvarova M, B. Tetu B et al. Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids // BMC Genomics. 2008;9. doi: 10.1186/1471-2164-9-99
F. Hirschhaeuser F, H. Menne H, C Dittfeld C et al. Multicellular tumor spheroids: An underestimated tool is catching up again // J. Biotechnol. 2010;148(1):3–15. doi: 10.1016/j.jbiotec.2010.01.012
Puls TJ, Tan X, Husain M et al. Development of a Novel 3D Tumor-tissue Invasion Model for High-throughput, High-content Phenotypic Drug Screening // Sci. Rep. 2018;8(1). doi:10.1038/s41598-018-31138-6
Jensen C, Teng Y. Is It Time to Start Transitioning From 2D to 3D Cell Culture? // Front Mol Biosci. 2010;7. doi:10.3389/fmolb.2020.00033
Rebecca VW, Somasundaram R, Herlyn M. Pre-clinical modeling of cutaneous melanoma // Nat Commun. 2020;11(1). doi:10.1038/s41467-020-15546-9
Pabiarzhyn VV, Pashinskaya ES, Semenov VM, Hancharou AY. Methodological aspects of setting up oncological models under experimental conditions // Vestn. Vitebsk State Med. Univ. 2018;17(6):32–45. doi: 10.22263/2312-4156.2018.6.32
Gilazieva Z, Ponomarev A, Rutland C et al. Promising applications of tumor spheroids and organoids for personalized medicine // Cancers. 2020;12(10):1–19. doi: 10.3390/cancers12102727
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
© АННМО «Вопросы онкологии», Copyright (c) 2021