Poster Presentation 25th Lorne Cancer Conference 2013

Investigating the role of exosomes in promoting melanoma metastasis. (#391)

Laura J Vella 1 , Bradley M Coleman 2 , Andrew F Hill 2 , Jonathan Cebon 1
  1. Ludwig Institute for Cancer Research, Heidelberg, VIC, Australia
  2. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne , Parkville, Victoria, Australia

Background: Exosomes are membrane bound microvesicles that are secreted by several cell types including tumours and have been found in biological fluids such as blood, CSF and urine. Exosomes are known to transfer protein and miRNA between neighbouring and distant cells, facilitating normal intracellular communication but also facilitating tumor communication within the local tumor microenvironment and distantly, mediating tumorigenesis. This study aimed to characterise exosomes released from metastatic melanoma patient cell lines and investigate the role exosomes have in mediating tumour heterogeneity.
Methods: Conditioned media from melanoma cell lines (established from fresh patient metastatic melanomas) was subject to ultracentrifugation and the exosomes subsequently characterised by protein composition, density and morphology. Functional assays included clonogenicity, motility & migration.
Results: Here, we characterise exosomes originating from a series of human patient metastatic melanoma cells lines. These cell lines are genotypically and phenotypically distinct enabling us to examine the role of exosomes in promoting intra-tumoral heterogeneity, facilitating drug resistance and metastasis and ultimately in driving tumour progression.
Conclusions: Melanomas comprise a complex heterogeneous collection of cells which show a high degree of plasticity, an effect that is proposed as being regulated by the microenvironment. We proposed that exosomes, a privileged source in the microenvironment of miRNA and protein that mirror the profile of the parent melanoma cell, enable cross talk between melanoma cells and contribute to tumour heterogeneity.