Extracellular vesicles secreted by highly metastatic clonal variants of osteosarcoma preferentially localize to the lungs and induce metastatic behaviour in poorly metastatic clones
| Autor: | Liliana Endo-Munoz, Haolu Wang, Sally Martin, Rebecca Macklin, Na Cai, Natalia Saenz Ponce, A. Cumming, Dorothy Loo, Kerry L. Inder, Rebecca E. Lane, Eleni Topkas, Nicholas A. Saunders |
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| Rok vydání: | 2016 |
| Předmět: |
Proteomics
0301 basic medicine Pathology medicine.medical_specialty Cell signaling Lung Neoplasms pre-metastatic niche Bone Neoplasms Cell Communication Receptors G-Protein-Coupled Metastasis Extracellular Vesicles 03 medical and health sciences Cell Movement Cell Line Tumor medicine Humans metastasis Neoplasm Invasiveness Cell Proliferation Osteosarcoma Cell growth business.industry medicine.disease Phenotype Clone Cells Gene Expression Regulation Neoplastic Microscopy Electron Microscopy Fluorescence Multiphoton 030104 developmental biology Oncology Cell culture Disease Progression Cancer research interclonal communication Signal transduction business Signal Transduction Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.9781 |
| Popis: | Osteosarcoma (OS) is the most common pediatric bone tumor and is associated with the emergence of pulmonary metastasis. Unfortunately, the mechanistic basis for metastasis remains unclear. Tumor-derived extracellular vesicles (EVs) have been shown to play critical roles in cell-to-cell communication and metastatic progression in other cancers, but their role in OS has not been explored. We show that EVs secreted by cells derived from a highly metastatic clonal variant of the KHOS cell line can be internalized by a poorly metastatic clonal variant of the same cell line and induce a migratory and invasive phenotype. This horizontal phenotypic transfer is unidirectional and provides evidence that metastatic potential may arise via interclonal co-operation. Proteomic analysis of the EVs secreted by highly metastatic OS clonal variants results in the identification of a number of proteins and G-protein coupled receptor signaling events as potential drivers of OS metastasis and novel therapeutic targets. Finally, multiphoton microscopy with fluorescence lifetime imaging in vivo, demonstrated a preferential seeding of lung tissue by EVs derived from highly metastatic OS clonal variants. Thus, we show that EVs derived from highly metastatic clonal variants of OS may drive metastatic behaviour via interclonal co-operation and preferential colonization of the lungs. |
| Databáze: | OpenAIRE |
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