N-Terminomics/TAILS of Tissue and Liquid Biopsies.

The N-terminomics approach of Terminal Amine Isotopic Labeling of Substrates (TAILS) enables the identification and quantification of natural and neo-N-termini of proteins using liquid chromatography and tandem mass spectrometry (LC-MS/MS). This methodology has been used to study protease function and identify protease substrates in cell culture systems, animal disease models, and more recently, has been applied to clinical samples. Here, we present the application of TAILS to tissue and liquid biopsies.

Matrix Metalloproteases as Influencers of the Cells' Social Media.

Matrix metalloproteinases (MMPs) have been studied in the context of cancer due to their ability to increase cell invasion, and were initially thought to facilitate metastasis solely through the degradation of the extracellular matrix (ECM). MMPs have also been investigated in the context of their ECM remodeling activity in several acute and chronic inflammatory diseases. However, after several MMP inhibitors failed in phase III clinical trials, a global reassessment of their biological functions was undertaken, which has revealed multiple unanticipated functions including the processing of chemokines, cytokines, and cell surface receptors.

N-Terminomics/TAILS Profiling of Proteases and Their Substrates in Ulcerative Colitis.

Dysregulated protease activity is often implicated in the initiation of inflammation and immune cell recruitment in gastrointestinal inflammatory diseases. Using N-terminomics/TAILS (terminal amine isotopic labeling of substrates), we compared proteases, along with their substrates and inhibitors, between colonic mucosal biopsies of healthy patients and those with ulcerative colitis (UC). Among the 1642 N-termini enriched using TAILS, increased endogenous processing of proteins was identified in UC compared to healthy patients.