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Extracellular Vesicle Membrane-Associated Proteins: Emerging Roles in Tumor Angiogenesis and Anti-Angiogenesis Therapy Resistance

Osteosarcoma-Derived Extracellular Vesicles Induce Lung Fibroblast Reprogramming

Department of Orthopedics, Balgrist University Hospital, CH-8008 Zurich, Switzerland
Institute for Biomechanics, ETH Zurich, CH-8008 Zurich, Switzerland
Department of Oncology, Children’s Research Center, University Children’s Hospital Zürich, CH-8032 Zurich, Switzerland
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(15), 5451;
Received: 9 July 2020 / Revised: 23 July 2020 / Accepted: 29 July 2020 / Published: 30 July 2020
(This article belongs to the Special Issue Extracellular Vesicles and Tumour Microenvironment)
Tumor-secreted extracellular vesicles (EVs) have been identified as mediators of cancer–host intercellular communication and shown to support pre-metastatic niche formation by modulating stromal cells at future metastatic sites. While osteosarcoma, the most common primary malignant bone tumor in children and adolescents, has a high propensity for pulmonary metastases, the interaction of osteosarcoma cells with resident lung cells remains poorly understood. Here, we deliver foundational in vitro evidence that osteosarcoma cell-derived EVs drive myofibroblast/cancer-associated fibroblast differentiation. Human lung fibroblasts displayed increased invasive competence, in addition to increased α-smooth muscle actin expression and fibronectin production upon EV treatment. Furthermore, we demonstrate, through the use of transforming growth factor beta receptor 1 (TGFBR1) inhibitors and CRISPR-Cas9-mediated knockouts, that TGFβ1 present in osteosarcoma cell-derived EVs is responsible for lung fibroblast differentiation. Overall, our study highlights osteosarcoma-derived EVs as novel regulators of lung fibroblast activation and provides mechanistic insight into how osteosarcoma cells can modulate distant cells to potentially support metastatic progression. View Full-Text
Keywords: osteosarcoma; extracellular vesicles; lung fibroblasts; tumor microenvironment; tumor-host interactions osteosarcoma; extracellular vesicles; lung fibroblasts; tumor microenvironment; tumor-host interactions
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MDPI and ACS Style

Mazumdar, A.; Urdinez, J.; Boro, A.; Migliavacca, J.; Arlt, M.J.E.; Muff, R.; Fuchs, B.; Snedeker, J.G.; Gvozdenovic, A. Osteosarcoma-Derived Extracellular Vesicles Induce Lung Fibroblast Reprogramming. Int. J. Mol. Sci. 2020, 21, 5451.

AMA Style

Mazumdar A, Urdinez J, Boro A, Migliavacca J, Arlt MJE, Muff R, Fuchs B, Snedeker JG, Gvozdenovic A. Osteosarcoma-Derived Extracellular Vesicles Induce Lung Fibroblast Reprogramming. International Journal of Molecular Sciences. 2020; 21(15):5451.

Chicago/Turabian Style

Mazumdar, Alekhya, Joaquin Urdinez, Aleksandar Boro, Jessica Migliavacca, Matthias J.E. Arlt, Roman Muff, Bruno Fuchs, Jess Gerrit Snedeker, and Ana Gvozdenovic. 2020. "Osteosarcoma-Derived Extracellular Vesicles Induce Lung Fibroblast Reprogramming" International Journal of Molecular Sciences 21, no. 15: 5451.

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