TY - JOUR
T1 - Functional imaging of legumain in cancer using a new quenched activity-based probe
AU - Edgington, Laura E.
AU - Verdoes, Martijn
AU - Ortega, Alberto
AU - Withana, Nimali P.
AU - Lee, Jiyoun
AU - Syed, Salahuddin
AU - Bachmann, Michael H.
AU - Blum, Galia
AU - Bogyo, Matthew
PY - 2013/1/9
Y1 - 2013/1/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84872113307&partnerID=8YFLogxK
U2 - https://doi.org/10.1021/ja307083b
DO - https://doi.org/10.1021/ja307083b
M3 - Article
C2 - 23215039
SN - 0002-7863
VL - 135
SP - 174
EP - 182
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 1
ER -