Induction of the intercellular adhesion molecule (ICAM-1) on squamous cell carcinoma by interferon gamma.
OBJECTIVE
To determine if the cell surface antigen, the intercellular adhesion molecule 1 (ICAM-1), is expressed on head and neck (H&N) squamous cell carcinoma (SCC) cell lines, and if treatment with interferon gamma (IFN-gamma) enhances the expression of the antigen. Intercellular adhesion molecule 1 mediates effector cell adhesion, activation, and function in inflammatory and immunologic reactions, and it may be important in the generation of antitumor immune surveillance and cytotoxicity against H&N SCC.


METHODS
Four human SCC cell lines, JHU-011-SCC, JHU-020-SCC, JHU-022-SCC, and FaDu, established by explant technique from tumors of the upper aerodigestive tract, were utilized for these experiments. The cell lines were maintained and tested under standard tissue culture conditions.


METHODS
Fluorescence-activated cell sorting and enzyme-linked immunosorbent assay were performed to identify the presence of ICAM-1 on the H&N SCC cell lines after staining with an anti-ICAM-1 monoclonal antibody (CD54). The SCC cell lines were treated with either fresh media or varying dosages (1 to 1000 U/mL) of recombinant human interferon gamma (rHuIFN-gamma) to determine constitutive and enhanced antigen expression. The kinetics of the response to rHuIFN-gamma were determined for the JHU-022-SCC cell line. The effect of the cytokines interleukin 1, interleukin 2, tumor necrosis factor alpha, and interferon alfa on ICAM-1 expression on JHU-022-SCC was also tested.


METHODS
Constitutive and enhanced ICAM-1 expression.


RESULTS
Low levels of constitutive expression of ICAM-1 were identified on all four H&N SCC cell lines, with significantly enhanced expression seen after rHuIFN-gamma treatment (P = .0001). Maximally enhanced expression of the antigen on JHU-022-SCC occurred after treatment for 48 hours with 100 U/mL of rHuIFN-gamma (P = .0001). Induction of ICAM-1 expression was detectable after treatment with as little as 10 U/mL of rHuIFN-gamma (P < .001). Induction was also present after treatment with interleukin 1 and tumor necrosis factor alpha, but not with interleukin 2 or interferon alfa.


CONCLUSIONS
Intercellular adhesion molecule 1 is constitutively expressed on H&N SCC cell lines, with enhanced expression seen after treatment with interferon gamma and other cytokines. This suggests that the antigen may be involved in the generation of an immune response against SCC of the H&N.
Scher
R L
RL
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Md.
Koch
W M
WM
Richtsmeier
W J
WJ
D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D016898:Interferon-alpha; D007375:Interleukin-1; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma