CD40 function in squamous cell cancer of the head and neck

Wenhui Cao; Lisa A. Cavacini; Karl C. Tillman; Marshall R. Posner

doi:10.1016/j.oraloncology.2004.11.005

CD40 function in squamous cell cancer of the head and neck

Wenhui Cao, Lisa A. Cavacini, Karl C. Tillman, Marshall R. Posner

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

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 PGE₂ but not IL-6, IL-10, FasL, GM-CSF, or TGFα. Co-ligation with EGFr further increased IL-8, VEGF and PGE₂ 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.

Original language	English
Pages (from-to)	462-469
Number of pages	8
Journal	Oral Oncology
Volume	41
Issue number	5
DOIs	https://doi.org/10.1016/j.oraloncology.2004.11.005
State	Published - May 2005
Externally published	Yes

Keywords

CD40
EGFr
Head and Neck Cancer
IL-8
PGE
VEGF

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10.1016/j.oraloncology.2004.11.005

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@article{37b61b453cbe4255b1566edb51301100,

title = "CD40 function in squamous cell cancer of the head and neck",

abstract = "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 PGE2 but not IL-6, IL-10, FasL, GM-CSF, or TGFα. Co-ligation with EGFr further increased IL-8, VEGF and PGE2 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.",

keywords = "CD40, EGFr, Head and Neck Cancer, IL-8, PGE, VEGF",

author = "Wenhui Cao and Cavacini, {Lisa A.} and Tillman, {Karl C.} and Posner, {Marshall R.}",

note = "Funding Information: Supported in part by donations to the Dana-Farber Cancer Institute from patients treated in the Head and Neck Oncology Program and from the Friends of the Dana-Farber Cancer Institute including a donation from the Elaine Promisel Siegel Restricted Fund; and the NIH: P01 DE12467 (MRP). We gratefully acknowledge J. Rheinwald, Brigham and Woman{\textquoteright}s Hospital and Harvard Skin Disease Research Center for providing human SCC cell lines and advice on our experimental design and Phillip Hines and Karl Munger, Harvard Medical School, for their advice. We also thank the former Immunex Corp. and Dr. William Dougall for providing CD40L for these experiments.",

year = "2005",

month = may,

doi = "10.1016/j.oraloncology.2004.11.005",

language = "English",

volume = "41",

pages = "462--469",

journal = "Oral Oncology",

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AU - Cao, Wenhui

AU - Cavacini, Lisa A.

AU - Tillman, Karl C.

AU - Posner, Marshall R.

N1 - Funding Information: Supported in part by donations to the Dana-Farber Cancer Institute from patients treated in the Head and Neck Oncology Program and from the Friends of the Dana-Farber Cancer Institute including a donation from the Elaine Promisel Siegel Restricted Fund; and the NIH: P01 DE12467 (MRP). We gratefully acknowledge J. Rheinwald, Brigham and Woman’s Hospital and Harvard Skin Disease Research Center for providing human SCC cell lines and advice on our experimental design and Phillip Hines and Karl Munger, Harvard Medical School, for their advice. We also thank the former Immunex Corp. and Dr. William Dougall for providing CD40L for these experiments.

PY - 2005/5

Y1 - 2005/5

N2 - 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 PGE2 but not IL-6, IL-10, FasL, GM-CSF, or TGFα. Co-ligation with EGFr further increased IL-8, VEGF and PGE2 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.

AB - 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 PGE2 but not IL-6, IL-10, FasL, GM-CSF, or TGFα. Co-ligation with EGFr further increased IL-8, VEGF and PGE2 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.

KW - CD40

KW - EGFr

KW - Head and Neck Cancer

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KW - PGE

KW - VEGF

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CD40 function in squamous cell cancer of the head and neck

Abstract

Keywords

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