Selective induction of cyclooxygenase-2 plays a role in lysophosphatidic acid regulated Fas ligand cell surface presentation

FEBS Lett. 2006 Jan 23;580(2):443-9. doi: 10.1016/j.febslet.2005.12.033. Epub 2005 Dec 20.

Abstract

Previous studies found that lysophosphatidic acid (LPA) upregulated Fas ligand (FasL) presentation on the ovarian cancer cell surface and lead to apoptosis of activated lymphocytes. In this report, we investigated the role of selective induction of cyclooxygenase-2 (Cox-2) in FasL cell surface presentation stimulated by LPA. Ovarian cancer cells pretreated with general aspirin derivative acetylsalicylic acid and specific Cox-2 inhibitor (NS-398) before stimulation with LPA, FasL cell surface presentation was significantly blocked, so was the apoptosis of activated lymphocytes mediated by increasing FasL on the ovarian cancer cell surface. Using the specific inhibitors PD98059, AG1478 or dominant-negative epidermal-growth-factor receptor (EGFR-DN) plasmid, we found that the activation of ERK1/2 played a role in Cox-2 induction, and the transactivation of EGFR worked as an upstream signaling pathway in ERK1/2 phosphorylation. This study first revealed the selective induction of Cox-2 by LPA led to FasL presentation on ovarian cancer cell surface and provide cancer cell immune privilege, and might provide important information of Cox-2 in cancer progression and Cox-2 inhibitors' application in cancer chemoprevention.

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens, Surface / metabolism*
  • Apoptosis / physiology
  • Aspirin / metabolism
  • Cell Line, Tumor
  • Cell Membrane / metabolism*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase Inhibitors / metabolism
  • Enzyme Activation
  • Enzyme Induction
  • Enzyme Inhibitors / metabolism
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fas Ligand Protein
  • Female
  • Flavonoids / metabolism
  • Humans
  • Lymphocyte Activation
  • Lymphocytes / metabolism
  • Lysophospholipids / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Nitrobenzenes / metabolism
  • Ovarian Neoplasms / immunology
  • Quinazolines
  • Signal Transduction / physiology
  • Sulfonamides / metabolism
  • Tumor Necrosis Factors / metabolism*
  • Tyrphostins / metabolism

Substances

  • Antigens, Surface
  • Cyclooxygenase Inhibitors
  • Enzyme Inhibitors
  • FASLG protein, human
  • Fas Ligand Protein
  • Flavonoids
  • Lysophospholipids
  • Membrane Glycoproteins
  • Nitrobenzenes
  • Quinazolines
  • Sulfonamides
  • Tumor Necrosis Factors
  • Tyrphostins
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • RTKI cpd
  • Cyclooxygenase 2
  • ErbB Receptors
  • Extracellular Signal-Regulated MAP Kinases
  • lysophosphatidic acid
  • Aspirin
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one