Functional imaging of legumain in cancer using a new quenched activity-based probe

Laura E. Edgington, Martijn Verdoes, Alberto Ortega, Nimali P. Withana, Jiyoun Lee, Salahuddin Syed, Michael H. Bachmann, Galia Blum, Matthew Bogyo

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

תקציר

Legumain is a lysosomal cysteine protease whose biological function remains poorly defined. Legumain activity is up-regulated in most human cancers and inflammatory diseases most likely as the result of high expression in populations of activated macrophages. Within the tumor microenvironment, legumain activity is thought to promote tumorigenesis. To obtain a greater understanding of the role of legumain activity during cancer progression and inflammation, we developed an activity-based probe that becomes fluorescent only upon binding active legumain. This probe is highly selective for legumain, even in the context of whole cells and tissues, and is also a more effective label of legumain than previously reported probes. Here we present the synthesis and application of our probe to the analysis of legumain activity in primary macrophages and in two mouse models of cancer. We find that legumain activity is highly correlated with macrophage activation and furthermore that it is an ideal marker for primary tumor inflammation and early stage metastatic lesions.

שפה מקוריתאנגלית אמריקאית
עמודים (מ-עד)174-182
מספר עמודים9
כתב עתJournal of the American Chemical Society
כרך135
מספר גיליון1
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 9 ינו׳ 2013

ASJC Scopus subject areas

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