ArticlePloS one2016
Tumor-Activated Mesenchymal Stromal Cells Promote Osteosarcoma Stemness and Migratory Potential via IL-6 Secretion.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed.
- Understanding and Overcoming Osteosarcoma Heterogeneity.Biomolecules · 2026Review
- Osteosarcoma as a communication-driven disease: redefining tumor-bone signaling networks as therapeutic targets.Frontiers in oncology · 2026Review
- Mesenchymal stroma drives axonogenesis and nerve-induced aggressiveness in osteosarcoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Microenvironment matters: insights from the FOSTER consortium on microenvironment-driven approaches to osteosarcoma therapy.Cancer metastasis reviews · 2025Review
- Article
- Endothelial remodeling in osteosarcomas: insights from patient samples and in vitro studies.American journal of cancer research · 2025Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Nε-(1-Carboxymethyl)-L-lysine/RAGE Signaling Drives Metastasis and Cancer Stemness through ERK/NFκB axis in Osteosarcoma.International journal of biological sciences · 2024Article
- Signal Pathways and microRNAs in Osteosarcoma Growth and the Dual Role of Mesenchymal Stem Cells in Oncogenesis.International journal of molecular sciences · 2023Review
- Cancer Stem Cells in Sarcomas: In Vitro Isolation and Role as Prognostic Markers: A Systematic Review.Cancers · 2023Review
- Mesenchymal stromal cells promote the drug resistance of gastrointestinal stromal tumors by activating the PI3K-AKT pathway via TGF-β2.Journal of translational medicine · 2023Article
- Endothelial Progenitor Cells Promote Osteosarcoma Progression and Invasiveness via AKT/PI3K Signaling.Cancers · 2023Article
- Endogenous Extracellular Matrix Regulates the Response of Osteosarcoma 3D Spheroids to Doxorubicin.Cancers · 2023Article
- Mesenchymal stem/stromal cells- a principal element for tumour microenvironment heterogeneity.Frontiers in immunology · 2023Review
- Tumor microenvironment enriches the stemness features: the architectural event of therapy resistance and metastasis.Molecular cancer · 2022Review
- The Role of Tumor Microenvironment in Regulating the Plasticity of Osteosarcoma Cells.International journal of molecular sciences · 2022Review
- Identification of novel prognostic biomarkers for osteosarcoma: a bioinformatics analysis of differentially expressed genes in the mesenchymal stem cells from single-cell sequencing data set.Translational cancer research · 2022Article
- Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters.International journal of molecular sciences · 2022Review
- Galectin-3 inhibition boosts the therapeutic efficacy of Semliki Forest virus in pediatric osteosarcoma.Molecular therapy oncolytics · 2022Article
- Genome-wide DNA methylation patterns reveal clinically relevant predictive and prognostic subtypes in human osteosarcoma.Communications biology · 2022Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma (OS) is an aggressive bone malignancy with a high relapse rate despite combined treatment with surgery and multiagent chemotherapy. As for other cancers, OS-associated microenvironment may contribute to tumor initiation, growth, and metastasis. We consider mesenchymal stromal cells (MSC) as a relevant cellular component of OS microenvironment, and have previously found that the interaction between MSC and tumor cells is bidirectional: tumor cells can modulate their peripheral environment that in turn becomes more favorable to tumor growth through metabolic reprogramming. Here, we determined the effects of MSC on OS stemness and migration, two major features associated with recurrence and chemoresistance. The presence of stromal cells enhanced the number of floating spheres enriched in cancer stem cells (CSC) of the OS cell population. Furthermore, the co-culturing with MSC stimulated the migratory capacity of OS via TGFβ1 and IL-6 secretion, and the neutralizing antibody anti-IL-6 impaired this effect. Thus, stromal cells in combination with OS spheres exploit a vicious cycle where the presence of CSC stimulates mesenchymal cytokine secretion, which in turn increases stemness, proliferation, migration, and metastatic potential of CSC, also through the increase of expression of adhesion molecules like ICAM-1. Altogether, our data corroborate the concept that a comprehensive knowledge of the interplay between tumor and stroma that also includes the stem-like fraction of tumor cells is needed to develop novel and effective anti-cancer therapies.
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