CD40 function in squamous cell cancer of the head and neck.
CD40 is expressed on basal keratinocytes and Squamous Cell Cancer of the Head and Neck (SCCHN) tumor cells in vivo and in vitro. CD40 ligation reduces proliferation of SCCHN cell lines and enhances EGFr mediated inhibition of proliferation. We investigated the mechanisms of CD40 function and EGFr cross-communication in SCCHN cell lines. CD40 ligation inhibited spontaneous and Fas-induced apoptosis. CD40 ligation specifically increased the secretion of IL-8, VEGF and PGE(2) but not IL-6, IL-10, FasL, GM-CSF, or TGFalpha. Co-ligation with EGFr further increased IL-8, VEGF and PGE(2) secretion. CD40 ligation also induced delayed activation and tyrosine phosphorylation of EGFr. CD40 induces secretion of specific proinflammatory and proangiogenic cytokines, inhibits spontaneous and Fas-induced apoptosis and increases EGFr phosphorylation. CD40 signaling may enhance the survival of SCCHN and tumor stroma.
Cao
Wenhui
W
Human Monoclonal Antibody Laboratory, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Cavacini
Lisa A
LA
Tillman
Karl C
KC
Posner
Marshall R
MR
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism / Q000502:physiology*; D023201:CD40 Ligand / Q000494:pharmacology; D002450:Cell Communication; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D053222:Fas Ligand Protein; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D018307:Neoplasms, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011453:Prostaglandins / Q000096:biosynthesis
D019013:CD40 Antigens; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011453:Prostaglandins; D023201:CD40 Ligand; D004815:Epidermal Growth Factor; D066246:ErbB Receptors