Cancers, Vol. 13, Pages 4697: Cathepsin S Evokes PAR2-Dependent Pain in Oral Squamous Cell Carcinoma Patients and Preclinical Mouse Models
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 immunolocalization of cathepsin S in human oral cancers suggests that carcinoma and macrophages generate cathepsin S in the oral cancer microenvironment. After cheek or paw injection, cathepsin S evoked nociception in wild-type mice but not in mice lacking PAR2 in Nav1.8-positive neurons (Par2Nav1.8), nor in mice treated with LY3000328 or an endogenous cathepsin S inhibitor (cystatin C). The human oral SCC cell line (HSC-3) with homozygous deletion of the gene for cathepsin S (CTSS) with CRISPR/Cas9 provoked significantly less mechanical allodynia and thermal hyperalgesia, as did those treated with LY3000328, compared to the control cancer mice. Our results indicate that cathepsin S is activated in oral SCC, and that cathepsin S contributes to cancer pain through PAR2 on neurons.
Source: Cancers - Category: Cancer & Oncology Authors: Nguyen Huu Tu Kenji Inoue Elyssa Chen Bethany M. Anderson Caroline M. Sawicki Nicole N. Scheff Hung D. Tran Dong H. Kim Robel G. Alemu Lei Yang John C. Dolan Cheng Z. Liu Malvin N. Janal Rocco Latorre Dane D. Jensen Nigel W. Bunnett Laura E. Edgington-Mit Tags: Article Source Type: research
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