Paracrine Signals from the Tumor Microenvironment Modulate Stem Cell Collagen Interaction and Remodeling, Indicating Early Functional Changes.
6 affiliations
- 1Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
- 2Center of Competence in Personalized Medicine, 3D and Telemedicine, Robotic Assisted and Minimally Invasive Surgery-"Leonardo da Vinci", 5800 Pleven, Bulgaria.
- 3Centre for Biomaterials and Tissue Engineering, Polytechnic University of Valencia, 46022 Valencia, Spain.
- 4Biomedical Research Center Networking in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain.
- 5Associate Project BG-RRP-2.004-0003, Medical University Pleven, 5800 Pleven, Bulgaria.
- 6Research Institute, Medical University Pleven, 5800 Pleven, Bulgaria.
Abstract
The tumor microenvironment (TME) is shaped by dynamic interactions between malignant cells and stromal components, with mesenchymal stem cells (MSCs) contributing to extracellular matrix (ECM) remodeling. Here, we examined how secretomes from two hematological cancer cell lines, RPMI-8226 (multiple myeloma) and HG-3 (B-cell leukemia), influence early functional responses of human adipose-derived MSCs (AD-MSCs) and their interaction with and reorganization of collagen. Cancer-conditioned media accelerated MSC proliferation (~2-fold faster doubling time) and increased SA-β-galactosidase activity (~3-4-fold above control). Upon adhesion to collagen, treated MSCs displayed distinct morphologies and reduced cell spreading (~2100 μm² vs. ~2500 μm² in controls), accompanied by altered collagen organization. To quantify collagen remodeling, we introduced the collagen removal index (CRI), expressing reorganized collagen area relative to cell spreading area. CRI revealed higher remodeling efficiency in HG-3-treated MSCs than in RPMI-8226-treated and control cells, indicating enhanced collagen-interacting capacity. Secretome exposure also modulated cytokine secretion, with increased bFGF under both conditions and IL-6 upregulation specifically following HG-3 exposure. After secretome withdrawal, most functional alterations, including senescence-associated changes, motility, and elevated bFGF, persisted. Notably, IL-6 upregulation and increased CRI emerged in RPMI-8226-exposed MSCs after withdrawal, suggesting a delayed response. Together, these findings reveal early, partially persistent functional shifts in MSC behavior and collagen remodeling that may represent an early stromal response with potential relevance to tumor progression.
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BibTeX
@article{topalova2026paracrine,
title = {{Paracrine Signals from the Tumor Microenvironment Modulate Stem Cell Collagen Interaction and Remodeling, Indicating Early Functional Changes.}},
author = {Lora Topalova and Tanya Stoyanova and Nadia García-Parra and José Luis Gómez Ribelles and Svetla Todinova and George Altankov},
journal = {Cells},
year = {2026},
month = sep,
doi = {10.3390/cells15191775},
url = {https://europepmc.org/article/MED/42882473},
note = {CC BY},
}
RIS
TY - JOUR
TI - Paracrine Signals from the Tumor Microenvironment Modulate Stem Cell Collagen Interaction and Remodeling, Indicating Early Functional Changes.
AU - Lora Topalova
AU - Tanya Stoyanova
AU - Nadia García-Parra
AU - José Luis Gómez Ribelles
AU - Svetla Todinova
AU - George Altankov
PY - 2026
DA - 2026/09/29
JO - Cells
DO - 10.3390/cells15191775
UR - https://europepmc.org/article/MED/42882473
AB - The tumor microenvironment (TME) is shaped by dynamic interactions between malignant cells and stromal components, with mesenchymal stem cells (MSCs) contributing to extracellular matrix (ECM) remodeling. Here, we examined how secretomes from two hematological cancer cell lines, RPMI-8226 (multiple myeloma) and HG-3 (B-cell leukemia), influence early functional responses of human adipose-derived MSCs (AD-MSCs) and their interaction with and reorganization of collagen. Cancer-conditioned media accelerated MSC proliferation (~2-fold faster doubling time) and increased SA-β-galactosidase activity (~3-4-fold above control). Upon adhesion to collagen, treated MSCs displayed distinct morphologies and reduced cell spreading (~2100 μm² vs. ~2500 μm² in controls), accompanied by altered collagen organization. To quantify collagen remodeling, we introduced the collagen removal index (CRI), expressing reorganized collagen area relative to cell spreading area. CRI revealed higher remodeling efficiency in HG-3-treated MSCs than in RPMI-8226-treated and control cells, indicating enhanced collagen-interacting capacity. Secretome exposure also modulated cytokine secretion, with increased bFGF under both conditions and IL-6 upregulation specifically following HG-3 exposure. After secretome withdrawal, most functional alterations, including senescence-associated changes, motility, and elevated bFGF, persisted. Notably, IL-6 upregulation and increased CRI emerged in RPMI-8226-exposed MSCs after withdrawal, suggesting a delayed response. Together, these findings reveal early, partially persistent functional shifts in MSC behavior and collagen remodeling that may represent an early stromal response with potential relevance to tumor progression.
SN - 2073-4409
ER -