Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/18188
Title: Intercellular Resistance to BRAF Inhibition Can Be Mediated by Extracellular Vesicle-Associated PDGFRβ.
Authors: Vella, Laura J;Behren, Andreas;Coleman, Bradley;Greening, David W;Hill, Andrew F;Cebon, Jonathan
Affiliation: Olivia Newton John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australia
The Florey Institute for Neuroscience and Mental Health, Parkville, VIC, Australia
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia
School of Cancer Medicine, La Trobe University, Heidelberg, VIC, Australia
Issue Date: Nov-2017
EDate: 2017-11-19
Citation: Neoplasia (New York, N.Y.) 2017; 19(11): 932-940
Abstract: Treatment of BRAF mutant melanoma with kinase inhibitors has been associated with rapid tumor regression; however, this clinical benefit is short-lived, and most patients relapse. A number of studies suggest that the extracellular environment promotes BRAF inhibitor resistance and tumor progression. Extracellular vesicles, such as exosomes, are functional mediators in the extracellular environment. They are small vesicles known to carry a concentrated group of functional cargo and serve as intercellular communicators not only locally but also systemically. Increasingly, it is reported that extracellular vesicles facilitate the development of drug resistance in cancer; however, their role in BRAF inhibitor resistance in melanoma is unclear. Here we investigated if extracellular vesicles from BRAF inhibitor-resistant melanoma could influence drug sensitivity in recipient melanoma cells. We demonstrate that the resistance driver, PDGFRβ, can be transferred to recipient melanoma cells via extracellular vesicles, resulting in a dose-dependent activation of PI3K/AKT signaling and escape from MAPK pathway BRAF inhibition. These data suggest that the BRAF inhibitor-sensitive phenotype of metastatic melanoma can be altered by delivery of PDGFRβ by extracellular vesicles derived from neighboring drug-resistant melanoma cells.
URI: http://ahro.austin.org.au/austinjspui/handle/1/18188
DOI: 10.1016/j.neo.2017.07.002
ORCID: 0000-0001-5329-280X
PubMed URL: 28963969
Type: Journal Article
Appears in Collections:Journal articles

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