Protein secretome analysis of evolving and responding tumor ecosystems

In the tumor ecosystem, we recognize local and distant environments, and the circulation through which the exchange of messages occurs. Communication is largely mediated through secretory protein signals and non-conventional secretory mechanisms such as the release of extracellular vesicles containing protein and RNA payloads. A plethora of antibody microarrays and mass spectrometry platforms are available to perform protein secretome analysis. Further application of nanomaterials will improve sensitivity and robustness to detect low-abundance proteins. The term tumor secretome is very broad; by using the ecosystem concept we introduce different in vivo and ex vivo sample types that can be employed for proteomics. These include tumor interstitial fluid (TIF), tumor proximal body fluids, organotypic tissue slices and exposure of a fresh surgical specimen to biotinylation, followed by streptavidin precipitation. In vitro models may mimic the tumor ecosystem or can be simplified by incorporating one cell type from the tumor ecosystem. We believe that models allowing the study of secretomes from tumor ecosystems will provide us insights in tumor biology, biomarkers (prognostic/predictive) and novel therapeutic targets