TLR4 signaling induces B7-H1 expression through MAPK pathways in bladder cancer cells

Cancer Invest. 2008 Oct;26(8):816-21. doi: 10.1080/07357900801941852.

Abstract

TLR4 (Toll-like receptor 4) and B7-H1, which were known to be restricted to immune cells in the past, were found to be aberrantly expressed in a majority of tumor cells, facilitating tumor evasion from immune surveillance. Our study demonstrated that activation of TLR4 signaling in bladder cancer cells up-regulated B7-H1 expression. Furthermore, this regulation was significantly attenuated by ERK or JNK inhibitor. Our results elucidated the molecule mechanism of regulation of B7-H1 expression through TLR4 signaling and may suggest new strategies of down-regulating the cancer-associated B7-H1 expression for bladder cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology
  • Antigens, CD / biosynthesis*
  • Antigens, CD / genetics
  • B7-H1 Antigen
  • Carcinoma, Transitional Cell / metabolism*
  • Carcinoma, Transitional Cell / pathology
  • Cell Line, Tumor
  • Chromones / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • Flavonoids / pharmacology
  • Humans
  • Imidazoles / pharmacology
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / physiology
  • Lipopolysaccharide Receptors / physiology
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Morpholines / pharmacology
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Processing, Post-Translational / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyridines / pharmacology
  • Toll-Like Receptor 4 / physiology*
  • Up-Regulation / drug effects
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Anthracenes
  • Antigens, CD
  • B7-H1 Antigen
  • CD274 protein, human
  • Chromones
  • Flavonoids
  • Imidazoles
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Morpholines
  • Neoplasm Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Pyridines
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • lipopolysaccharide, Escherichia coli O111 B4
  • pyrazolanthrone
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one