Exploring the Role of Osteosarcoma-Derived Extracellular Vesicles in Pre-Metastatic Niche Formation and Metastasis in the 143-B Xenograft Mouse Osteosarcoma Model.

The pre-metastatic niche (PMN) is a tumor-driven microenvironment in distant organs that can foster and support the survival and growth of disseminated tumor cells. This facilitates the establishment of secondary lesions that eventually form overt metastasis, the main cause of cancer-related death. In recent years, tumor-derived extracellular-vesicles (EVs) have emerged as potentially key drivers of the PMN.

Comparative Degradomics of Porcine and Human Wound Exudates Unravels Biomarker Candidates for Assessment of Wound Healing Progression in Trauma Patients.

Impaired cutaneous wound healing is a major complication in elderly people and patients suffering from diabetes, the rate of which is rising in industrialized countries. Heterogeneity of clinical manifestations hampers effective molecular diagnostics and decisions for appropriate therapeutic regimens. Using a customized positional quantitative proteomics workflow, we have established a time-resolved proteome and N-terminome resource from wound exudates in a clinically relevant pig wound model that we exploited as a robust template to interpret a heterogeneous dataset from patients undergoing the same wound treatment.

Time-Resolved Analysis of Matrix Metalloproteinase Substrates in Complex Samples.

Identification of physiological substrates is the key to understanding the pleiotropic functions of matrix metalloproteinases (MMPs) in health and disease. Quantitative mass spectrometry-based proteomics has revolutionized current approaches in protease substrate discovery and helped to unravel many new MMP activities in complex biological systems. Multiplexing further extended the capabilities of these techniques and facilitated more complicated experimental designs that include multiple proteases or monitoring the activity of a single protease at more than one concentration or at multiple time points with a complex test proteome.

In vivo assessment of protease dynamics in cutaneous wound healing by degradomics analysis of porcine wound exudates.

Proteases control complex tissue responses by modulating inflammation, cell proliferation and migration, and matrix remodeling. All these processes are orchestrated in cutaneous wound healing to restore the skin's barrier function upon injury. Altered protease activity has been implicated in the pathogenesis of healing impairments, and proteases are important targets in diagnosis and therapy of this pathology.

Time-resolved analysis of the matrix metalloproteinase 10 substrate degradome.

Proteolysis is an irreversible post-translational modification that affects intra- and intercellular communication by modulating the activity of bioactive mediators. Key to understanding protease function is the system-wide identification of cleavage events and their dynamics in physiological contexts. Despite recent advances in mass spectrometry-based proteomics for high-throughput substrate screening, current approaches suffer from high false positive rates and only capture single states of protease activity.