A role for HMGB1, HSP60 and Myd88 in growth of murine mammary carcinoma in vitro

Cell Immunol. 2013 Apr;282(2):136-45. doi: 10.1016/j.cellimm.2013.04.014. Epub 2013 May 14.

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.

Keywords: 4T1; Breast cancer; HMGB1; HSP60; Myd88.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation*
  • Chaperonin 60 / genetics*
  • Chaperonin 60 / immunology
  • Chaperonin 60 / metabolism
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • HMGB1 Protein / genetics*
  • HMGB1 Protein / immunology
  • HMGB1 Protein / metabolism
  • Mammary Neoplasms, Animal / genetics
  • Mammary Neoplasms, Animal / metabolism
  • Mammary Neoplasms, Animal / pathology
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Myeloid Differentiation Factor 88 / antagonists & inhibitors
  • Myeloid Differentiation Factor 88 / genetics*
  • Myeloid Differentiation Factor 88 / metabolism
  • Peptides / pharmacology
  • RNA Interference
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism

Substances

  • Antibodies, Neutralizing
  • Chaperonin 60
  • Chemokine CCL2
  • HMGB1 Protein
  • Myeloid Differentiation Factor 88
  • Peptides
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Matrix Metalloproteinase 9