A Degradomic Landscape of Proteolytic Remodeling in Melanoma Lung Metastasis
Camila Eduarda Alves Martins Nogueira, Fabiana Olímpio, Murilo Salardani, Uilla Barcick, Luis Roberto Fonseca, Flávio Aimbire, Letícia Dias Lima Jedlicka, Flávio V. Loures, Luciane Portas Capelo, Valdeci Lima, Taysa Monteiro de Oliveira, Bianca C. S. C. Barros
TL;DR
This study maps proteolytic changes in melanoma lung metastasis, identifying key enzymes and patterns across different compartments.
Contribution
The work provides a multicompartment degradomic resource for melanoma lung metastasis, revealing novel proteolytic signatures and enzyme contributions.
Findings
Over 8,000 semitryptic peptides were identified, with the secretome showing the highest cleavage burden.
Distinct cleavage-site motifs were found in tissue, plasma, and secretome, implicating specific proteases like MMP2 and cathepsins.
Proteolytic remodeling impacts extracellular matrix, inflammation, and metabolism in metastatic niches.
Abstract
Melanoma metastasis involves extensive remodeling of the tumor microenvironment, yet the proteolytic processes underlying pulmonary colonization remain poorly defined. Using the B16F10 intravenous melanoma model in C57BL/6J mice, we performed an integrative degradomic analysis of metastatic lung tissue, plasma, and secretome of early passaged primary cultures derived from metastatic foci. Semispecific database searches identified nearly 8,000 semitryptic peptides across compartments, with the secretome exhibiting the highest burden of cleavage events, indicating an intensely proteolytic microenvironment. Cleavage profiles were compartment-specific, dominated by actin in metastatic lung tissue, α2-macroglobulin in plasma, and SPARC in the secretome. Cleavage-site motif analysis revealed conserved His/Ser (P1/P1′) preferences in tissue and plasma, whereas the secretome showed a distinct…
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Taxonomy
TopicsAdvanced Proteomics Techniques and Applications · Peptidase Inhibition and Analysis · Protease and Inhibitor Mechanisms