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Sarah E Coupland, Sam Prendergast, Martina Angi, Deborah Simpson, Robert Beynon, Helen Kalirai; Proteomic analysis of uveal melanoma (UM) secretome reveals novel biological insights and potential biomarkers.. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© 2017 Association for Research in Vision and Ophthalmology.
Proteins secreted or shed from cancer cells, the “cancer secretome”, represent an important class of bioactive molecules thought to play a causal role in cancer progression. We investigated the UM secretome as a source of biomarkers of early metastatic disease and its capacity to provide novel insights into tumour biology.
Secretomes of short-term UM cultures established from patient tumours with a high- (HR; n=10) or low- (LR; n=4) metastatic risk were analysed using nanoLC-MS/MS-based label-free quantitative proteomics. They were compared with the secretomes of normal cultured choroidal melanocytes (NCM; n=5). Protein identification was performed using Proteome Discover v3.1 and protein quantification was undertaken using Progenesis®v2.0. Bioinformatics analyses applied SecretomeP.v2.0, SignalP.v4.1, Exocarta.v5 and Ingenuity® Pathway Analysis (IPA).
Initial analysis produced a dataset of 1843 proteins, which were common to all three analysed subgroups (HR, LR, NCM). Of these, 758 proteins with ≥3 unique peptides were identified. These 758 proteins could be subdivided into: 25% classically/non-classically secreted, 46% exosomal proteins, and 29% other. Taking only the 538 proteins into account that were secreted by classical, non-classical or exosomal mechanisms, IPA suggested that they have biological involvement in cell proliferation, growth and movement. Further, IPA highlighted top canonical signalling pathway involvement of these proteins, particularly associated with hepatic fibrosis/hepatic stellate cell activation and the mTORC1-S6K axis. Finally, CCN Family Member 3 and Neuropilin 2, both previously shown in cancer to promote metastasis, were highly upregulated in HR vs LR UM.
UM secretome analysis identified cancer-associated proteins likely to represent important biomarkers of disease and/or play a functional role in disease progression. Exosomes are a likely mode of local and distal communication in UM.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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