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Abstract <p><b>Objective:</b> One of the major challenges in contemporary oncology is tumor recurrence after seemingly successful therapy, with metastasis—including to bone—being a frequent manifestation. Bone provides a unique microenvironment enriched with mesenchymal stem cells (MSCs) that produce extracellular matrix (ECM), which not only offers structural support but also regulates cell migration, proliferation, and differentiation. <b>Methods:</b> In this study, we employed extracellular matrices derived from human embryonic bone marrow mesenchymal stem cells (FetMSC) and investigated their effects on colorectal carcinoma (Caco-2) and osteosarcoma (HOS) cell lines. <b>Results:</b> Culturing both tumor cell types on FetMSC-derived ECM led to a marked inhibition of proliferation, accompanied by G<sub>0</sub>/G<sub>1</sub> cell cycle arrest, activation of autophagy, and enhanced migratory potential. These changes were associated with increased expression of epithelial-to-mesenchymal transition (EMT) and stemness markers.Furthermore, tumor cells incubated on FetMSC-derived ECM exhibited increased resistance to anticancer drugs. <b>Conclusion:</b> Collectively, our findings indicate that mesenchymal-derived extracellular matrix functions as an active regulator of tumor cell behavior, capable of inducing a dormant-like state, promoting chemoresistance, and potentially supporting subsequent tumor regrowth.</p>

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The Hidden Niche: MSC Extracellular Matrix as a Regulator of Tumor Quiescence, Migration and Antidrug Resistance of Tumor Cells to Therapy

  • 期刊论文

  • 发表日期：

    2025年12月29日

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  • Marina A. Mikeladze,
  • Margarita A. Galcheva,
  • Nikolay D. Aksenov,
  • Irina V. Guzhova

摘要

Abstract

Objective: One of the major challenges in contemporary oncology is tumor recurrence after seemingly successful therapy, with metastasis—including to bone—being a frequent manifestation. Bone provides a unique microenvironment enriched with mesenchymal stem cells (MSCs) that produce extracellular matrix (ECM), which not only offers structural support but also regulates cell migration, proliferation, and differentiation. Methods: In this study, we employed extracellular matrices derived from human embryonic bone marrow mesenchymal stem cells (FetMSC) and investigated their effects on colorectal carcinoma (Caco-2) and osteosarcoma (HOS) cell lines. Results: Culturing both tumor cell types on FetMSC-derived ECM led to a marked inhibition of proliferation, accompanied by G0/G1 cell cycle arrest, activation of autophagy, and enhanced migratory potential. These changes were associated with increased expression of epithelial-to-mesenchymal transition (EMT) and stemness markers.Furthermore, tumor cells incubated on FetMSC-derived ECM exhibited increased resistance to anticancer drugs. Conclusion: Collectively, our findings indicate that mesenchymal-derived extracellular matrix functions as an active regulator of tumor cell behavior, capable of inducing a dormant-like state, promoting chemoresistance, and potentially supporting subsequent tumor regrowth.