Extracellular vesicles secreted by highly metastatic clonal variants of osteosarcoma preferentially localize to the lungs and induce metastatic behaviour in poorly metastatic clones

Macklin, Rebecca, Wang, Haolu, Loo, Dorothy, Martin, Sally, Cumming, Andrew, Cai, Na, Lane, Rebecca, Ponce, Natalia Saenz, Topkas, Eleni, Inder, Kerry, Saunders, Nicholas A. and Endo-Munoz, Liliana (2016) Extracellular vesicles secreted by highly metastatic clonal variants of osteosarcoma preferentially localize to the lungs and induce metastatic behaviour in poorly metastatic clones. Oncotarget, 7 28: 43570-43587. doi:10.18632/oncotarget.9781


Author Macklin, Rebecca
Wang, Haolu
Loo, Dorothy
Martin, Sally
Cumming, Andrew
Cai, Na
Lane, Rebecca
Ponce, Natalia Saenz
Topkas, Eleni
Inder, Kerry
Saunders, Nicholas A.
Endo-Munoz, Liliana
Title Extracellular vesicles secreted by highly metastatic clonal variants of osteosarcoma preferentially localize to the lungs and induce metastatic behaviour in poorly metastatic clones
Journal name Oncotarget   Check publisher's open access policy
ISSN 1949-2553
Publication date 2016-06-02
Year available 2016
Sub-type Article (original research)
DOI 10.18632/oncotarget.9781
Open Access Status DOI
Volume 7
Issue 28
Start page 43570
End page 43587
Total pages 18
Place of publication Albany, NY, United States
Publisher Impact Journals LLC
Collection year 2017
Language eng
Formatted abstract
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.
Keyword Extracellular vesicles
Interclonal communication
Metastasis
Osteosarcoma
Pre-metastatic niche
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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