1. A role for HMGB1, HSP60 and Myd88 in growth of murine mammary carcinoma in vitro
- Author
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Robert A. Kurt, Antonio Serrano, Kyle C. Tucker, Jacob M. Ricca, Samantha A. Chalmers, Jason Ewer, Caroline Vail, and Alec Eidelman
- Subjects
Immunology ,Blotting, Western ,Receptor for Advanced Glycation End Products ,chemical and pharmacologic phenomena ,Apoptosis ,Mammary Neoplasms, Animal ,Biology ,HMGB1 ,Article ,Mice ,RNA interference ,Cell Line, Tumor ,Animals ,HMGB1 Protein ,Receptors, Immunologic ,Receptor ,Chemokine CCL2 ,Cell Proliferation ,Cell growth ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Cycle ,hemic and immune systems ,Chaperonin 60 ,Cell cycle ,respiratory system ,Antibodies, Neutralizing ,In vitro ,Toll-Like Receptor 2 ,body regions ,Gene Expression Regulation, Neoplastic ,Toll-Like Receptor 4 ,Matrix Metalloproteinase 9 ,Tumor progression ,Myeloid Differentiation Factor 88 ,biology.protein ,Cancer research ,RNA Interference ,Peptides - Abstract
Previously we reported that Myd88 contributed to tumor progression. To begin to decipher what may be inducing Myd88 dependent signaling we focused on proteins that could function as damage associated molecular pattern molecules (DAMPs) since DAMPs have been reported to be secreted by tumors, and certain DAMPs mediate effects through toll-like receptors. A screen of mammary carcinoma for DAMP expression showed HMGB1 and HSP60 were significantly elevated relative to normal mammary epithelium, and targeting these DAMPs, or receptors for these DAMPs influenced growth of tumor cells. Moreover, analysis using a Myd88 inhibitory peptide suggested that HMGB1 mediated its effects in a Myd88 dependent manner, and inhibiting Myd88 function decreased HMGB1 and HSP60 gene expression. Collectively, these data suggest that HMGB1 and HSP60 contribute to growth of mammary carcinoma cells, HMGB1 accomplishes this, at least in part, through Myd88 dependent signaling, and these DAMPs are expressed in a Myd88 dependent manner.
- Published
- 2012