Research ArticleCancer

Multiepitope tissue analysis reveals SPPL3-mediated ADAM10 activation as a key step in the transformation of melanocytes

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Sci. Signal.  14 Mar 2017:
Vol. 10, Issue 470, eaai8288
DOI: 10.1126/scisignal.aai8288

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Mapping protein drivers of melanoma

Genomic profiling technology has identified purported driver mutations in various cancers, but it is most often the proteins that drive tumor development and present therapeutic targets. Furthermore, tumor genomic profiling misses the contribution of cells of the tumor microenvironment to tumor progression. Using multiepitope ligand cartography on human skin samples, Ostalecki et al. identified changes in protein abundance and subcellular localization in melanocytes and keratinocytes that were associated with various stages of melanoma development. The findings revealed the transfer of a peptidase-metalloproteinase pair from early-stage BRAF-mutant/PTEN-null melanoma cells to adjacent normal keratinocytes through cell contact. The recipient keratinocytes exhibited altered protein abundance and secretion. Inhibiting this intercellular mode of communication and its effects might be therapeutic in melanoma patients.