title: Surface membrane-expressed CD40 is present on tumor cells from squamous cell cancer of the head and neck in vitro and in vivo and regulates cell growth in tumor cell lines.
abstract: Because regional spread to lymph nodes without systemic spread is a relatively common event in squamous cell cancer of the head and neck (SCCHN), it is possible that lymphoid-related receptors or cytokines might directly impact the growth of these tumors. In the present study, we have shown by flow cytometry and Western blotting that the central lymphoid regulatory molecule, CD40, is expressed on the surface of all seven SCCHN tumor cell lines studied. Tumor cell lines also expressed epidermal growth factor (EGF) receptor, MHC class I, and CD95 (Fas) but did not uniformly express other important lymphoid regulatory molecules such as CD80, CD86, or interleukin (IL) 2 receptor components. CD40 ligation by trimeric CD40 ligand (CD40L) resulted in a 20-45% inhibition of tumor cell growth in three of seven cell lines tested. The cytokines IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-11, and IL-15 neither inhibited nor stimulated growth in any of the cell lines tested. EGF had pleiotropic effects on cell growth; it inhibited growth in two cell lines, stimulated growth in one cell line, and had no effect in four cell lines. When coligation by EGF and CD40L was studied, additive or supra-additive growth inhibition was seen in four cell lines. Three cell lines were unaffected by EGF, CD40, or coligation with both reagents. Examination of tumor tissues from 12 previously untreated patients representing a broad spectrum of patients presenting with SCCHN demonstrated CD40 expression in all 12 tumor specimens. This study supports the notion that CD40 is a regulatory molecule for the growth of SCCHN. The important role of CD40-CD40L interactions in the regulation of immune cells in the lymph node and the unique high-level expression of CD40L by these immune cells lend support to the hypothesis that this ligand/receptor pair is an important mediator of cell growth in SCCHN.
authors.affiliation: The Human Monoclonal Antibody Laboratory, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA. marshall_posner@dfci.harvard.edu
authors.forename: M R
authors.initials: MR
authors.lastname: Posner
authors.forename: L A
authors.initials: LA
authors.lastname: Cavacini
authors.forename: M P
authors.initials: MP
authors.lastname: Upton
authors.forename: K C
authors.initials: KC
authors.lastname: Tillman
authors.forename: E R
authors.initials: ER
authors.lastname: Gornstein
authors.forename: C M
authors.initials: CM
authors.lastname: Norris
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D019013:CD40 Antigens / Q000096:biosynthesis*; D023201:CD40 Ligand; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008562:Membrane Glycoproteins / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016207:Cytokines; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D016211:Transforming Growth Factor alpha; D023201:CD40 Ligand; D004815:Epidermal Growth Factor