Despite major improvements on the knowledge and clinical management, cancer is still a deadly disease. Novel biomarkers for better cancer detection, diagnosis and treatment prediction are urgently needed. Proteins secreted, shed or leaking from the cancer cell, collectively termed the cancer secretome, are promising biomarkers since they might be detectable in blood or other biofluids. Furthermore, the cancer secretome in part represents the tumor microenvironment that plays a key role in tumor promoting processes such as angiogenesis and invasion. The cancer secretome, sampled as conditioned medium from cell lines, tumor/tissue interstitial fluid or tumor proximal body fluids, can be studied comprehensively by nanoLC-MS/MS-based approaches. Here, we outline the importance of current cancer secretome research and describe the mass spectrometry-based analysis of the secretome. Further, we provide an overview of cancer secretome research with a focus on the three most common cancer types: lung, breast and colorectal cancer. We conclude that the cancer secretome research field is a young, but rapidly evolving research field. Up to now, the focus has mainly been on the discovery of novel promising secreted cancer biomarker proteins. An interesting finding that merits attention is that in cancer unconventional secretion, e.g. via vesicles, seems increased. Refinement of current approaches and methods and progress in clinical validation of the current findings are vital in order to move towards applications in cancer management. This article is part of a Special Issue entitled: An Updated Secretome.
Keywords: (M)PE; (malignant) pleural effusion; 1D-GE; 2D-(DI)GE; AC; CM; Cancer secretome; Clinical application; IHC; LC-MS/MS; MS; NAF; NIF; NSCLC; Proteomics; SCC; SCLC; SRM; Secreted protein biomarker; TIF; Tumor microenvironment; Unconventional secretion; WB; adenocarcinoma; conditioned medium; immunohistochemistry; liquid chromatography tandem mass spectrometry; mass spectrometry; miR; microRNA; nipple aspirate fluid; non-small cell lung cancer; normal interstitial fluid; one-dimensional gel electrophoresis; selected reaction monitoring; small cell lung cancer; squamous cell carcinoma; tumor/tissue interstitial fluid; two-dimensional (difference in) gel electrophoresis; western blot.
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