Klabukov I, Eygel D, Baranovskii DS. Integrin-driven differences in extracellular matrix regulation of 3D-cultured tumor cells. World J Gastrointest Oncol 2026; 18(10): 119474 [DOI: 10.4251/wjgo.119474]
Corresponding Author of This Article
Ilya Klabukov, PhD, Associate Professor, Head, Department of Regenerative Medicine, National Medical Research Radiological Center, 4 Koroleva Street, Obninsk 249036, Kaluzhskaya Oblast’, Russia. ilya.klabukov@gmail.com
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Cell & Tissue Engineering
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review-article
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Klabukov I, Eygel D, Baranovskii DS. Integrin-driven differences in extracellular matrix regulation of 3D-cultured tumor cells. World J Gastrointest Oncol 2026; 18(10): 119474 [DOI: 10.4251/wjgo.119474]
World J Gastrointest Oncol. Oct 15, 2026; 18(10): 119474 Published online Oct 15, 2026. doi: 10.4251/wjgo.119474
Integrin-driven differences in extracellular matrix regulation of 3D-cultured tumor cells
Ilya Klabukov, Daria Eygel, Denis S Baranovskii
Ilya Klabukov, Daria Eygel, Denis S Baranovskii, Department of Regenerative Medicine, National Medical Research Radiological Center, Obninsk 249036, Kaluzhskaya Oblast’, Russia
Ilya Klabukov, Obninsk Institute for Nuclear Power Engineering, National Research Nuclear University MEPhI, Obninsk 249033, Kaluzhskaya Oblast’, Russia
Denis S Baranovskii, Institute of Systems Biology and Medicine, Russian University of Medicine, Moscow 127473, Moskva, Russia
Author contributions: Klabukov I conceptualized and designed the research, wrote the manuscript, and revised the manuscript; Baranovskii DS and Eygel D analyzed the data. All authors approved the final published version of the manuscript.
AI contribution statement: DeepL service was used for grammar polishing.
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
Corresponding author: Ilya Klabukov, PhD, Associate Professor, Head, Department of Regenerative Medicine, National Medical Research Radiological Center, 4 Koroleva Street, Obninsk 249036, Kaluzhskaya Oblast’, Russia. ilya.klabukov@gmail.com
Received: January 28, 2026 Revised: February 18, 2026 Accepted: May 14, 2026 Published online: October 15, 2026 Processing time: 231 Days and 10.4 Hours
Abstract
The differences in the regulation of 3D-cultured mesenchymal and epithelial cell lines are driven by a wide range of endogenous and exogenous factors. Recently published transcriptomic studies have demonstrated that these differences are, in part, associated with extracellular matrix (ECM) properties and ECM-related cellular factors. Based on these studies, we propose that the dysregulation of specific genes involved in epithelial-mesenchymal transition, including CD44, ALDH1A1, PROM1, CDH1, VIM, and ZEB1, may also influence interactions between cells and the newly synthesized ECM within tumor spheroids. These interactions may be directly affected by the density and spatial distribution of integrins on the cell membrane, potentially explaining differences between newly synthesized scaffolds in 3D spheroids and the native ECM. This review aims to discuss the factors underlying integrin-mediated regulatory differences among 3D-cultured cells with heterogeneous phenotypes.
Core Tip: Differences in gene regulation between 3D-cultured mesenchymal and epithelial cells extend beyond the epithelial-mesenchymal transition and influence how tumor cells interact with newly synthesized extracellular matrix. The regulation of integrin density and spatial distribution appears to play a central role in mediating cell-extracellular matrix interactions and may help explain the distinct behaviors observed among different tumor tissue models.
