Journal article
Cathepsin s evokes par2-dependent pain in oral squamous cell carcinoma patients and preclinical mouse models
NH Tu, K Inoue, E Chen, BM Anderson, CM Sawicki, NN Scheff, HD Tran, DH Kim, RG Alemu, L Yang, JC Dolan, CZ Liu, MN Janal, R Latorre, DD Jensen, NW Bunnett, LE Edgington-Mitchell, BL Schmidt
Cancers | Published : 2021
Abstract
Oral squamous cell carcinoma (SCC) pain is more prevalent and severe than pain gener-ated by any other form of cancer. We previously showed that protease-activated receptor-2 (PAR2) contributes to oral SCC pain. Cathepsin S is a lysosomal cysteine protease released during injury and disease that can activate PAR2. We report here a role for cathepsin S in PAR2-dependent cancer pain. We report that cathepsin S was more active in human oral SCC than matched normal tissue, and in an orthotopic xenograft tongue cancer model than normal tongue. The multiplex immuno-localization of cathepsin S in human oral cancers suggests that carcinoma and macrophages gener-ate cathepsin S in the oral cancer mic..
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Awarded by University of Melbourne
Funding Acknowledgements
Supported by grants from the National Institutes of Health (NS102722, DE026806, DK118971, DE029951, N.W.B., B.L.S.) and Department of Defense (W81XWH1810431, N.W.B., B.L.S.). L.E.M. was supported by a Priority-Driven Collaborative Cancer Research grant (co-funded by Cancer Australia and Cure Cancer, GNT1157171), a Grimwade Fellowship from the Russell and Mab Grimwade Miegunyah Fund at The University of Melbourne, and a DECRA Fellowship from the Australian Research Council (ARC, DE180100418).