Feasibility Study of an Assay Measuring Activity of Oral Cancer Protease Mixtures to Cleave Protease-Activated Receptor 2, an Oral Cancer Pain Mediator
- 1Translational Research Center, NYU Dentistry, New York, NY 10010, USA
- 2Department of Medicine, NYU Langone Health, New York, NY 10016, USA
- 3Translational Research Center and the Pain Research Center, NYU Dentistry, New York, NY 10010, USA
Abstract
Oral cancer patients suffer pain that is patient-specific and heterogeneous at the site of the tumor. Protease-activated receptor 2 (PAR2), a G-protein coupled receptor and an oral cancer mediator, is activated by protease cleavage of an N-terminal ligand. Once cleaved, the receptor is retained at the plasma membrane or re-distributed (trafficking) to internal sites followed by downstream protease-specific signaling. The oral cancer tumor microenvironment (TME) is replete with protases that activate PAR2, potentially evoking PAR2 trafficking and signaling that is unique to each cancer and reflecting the protease composition of the individual TMEs. To measure PAR2 cleavage activity in oral cancer samples, an array of overlapping peptides spanning the PAR2 N-terminus was assembled. In this feasibility study, we assayed the cleavage activity of individual PAR2-activating proteases and mixtures of proteases modeling the oral cancer TME. Additionally, we confirmed that PAR2-cleaving proteases are active in oral cancer patient saliva, a sample that can be collected non-invasively to measure PAR2 cleavage in patients when they are experiencing pain prior to surgery. Further studies should elucidate the utility of the peptide array to measure PAR2-activating proteolysis in cancer samples.
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BibTeX
@article{ramirezgarcia2026feasibility,
title = {{Feasibility Study of an Assay Measuring Activity of Oral Cancer Protease Mixtures to Cleave Protease-Activated Receptor 2, an Oral Cancer Pain Mediator}},
author = {Paulina D. Ramirez-Garcia and Igor Dolgalev and Sarah Zubli and Brian L. Schmidt and Donna G. Albertson},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27208971},
url = {https://www.mdpi.com/1422-0067/27/20/8971},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Feasibility Study of an Assay Measuring Activity of Oral Cancer Protease Mixtures to Cleave Protease-Activated Receptor 2, an Oral Cancer Pain Mediator
AU - Paulina D. Ramirez-Garcia
AU - Igor Dolgalev
AU - Sarah Zubli
AU - Brian L. Schmidt
AU - Donna G. Albertson
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27208971
UR - https://www.mdpi.com/1422-0067/27/20/8971
AB - Oral cancer patients suffer pain that is patient-specific and heterogeneous at the site of the tumor. Protease-activated receptor 2 (PAR2), a G-protein coupled receptor and an oral cancer mediator, is activated by protease cleavage of an N-terminal ligand. Once cleaved, the receptor is retained at the plasma membrane or re-distributed (trafficking) to internal sites followed by downstream protease-specific signaling. The oral cancer tumor microenvironment (TME) is replete with protases that activate PAR2, potentially evoking PAR2 trafficking and signaling that is unique to each cancer and reflecting the protease composition of the individual TMEs. To measure PAR2 cleavage activity in oral cancer samples, an array of overlapping peptides spanning the PAR2 N-terminus was assembled. In this feasibility study, we assayed the cleavage activity of individual PAR2-activating proteases and mixtures of proteases modeling the oral cancer TME. Additionally, we confirmed that PAR2-cleaving proteases are active in oral cancer patient saliva, a sample that can be collected non-invasively to measure PAR2 cleavage in patients when they are experiencing pain prior to surgery. Further studies should elucidate the utility of the peptide array to measure PAR2-activating proteolysis in cancer samples.
SN - 1422-0067
ER -