Effects of cisplatin, alpha-interferon, and 13-cis retinoic acid on the expression of Fas (CD95), intercellular adhesion molecule-1 (ICAM-1), and epidermal growth factor receptor (EGFR) in oral cancer cell lines.
BACKGROUND
Previous studies showed that many chemotherapeutic agents can induce immuno-suppression at therapeutic drug concentrations whereas low drug doses induce immuno-augmentation.


METHODS
The effect of low-dose cisplatin, interferon-alpha, and 13-cis retinoic acid on receptors involved in immune-mediated apoptosis (Fas/CD95), cell growth (epidermal growth factor receptor) and lymphocyte adhesion (intercellular adhesion molecule-1) was investigated in two oral cancer cell lines (UT-SCC-20A and UT-SCC-24A). Different methods for cell preparation were studied: mechanical and enzymatic detachment, and culture on chamber slides. Receptor expression was investigated using immunohistochemical staining. The amount of soluble and cell-bound Fas was determined with the ELISA technique, and the functional relevance of Fas expression, apoptosis induction, was analyzed.


RESULTS
Cisplatin enhanced cytoplasm and membrane staining for Fas in both cell lines. After cisplatin treatment, the amount of soluble Fas was increased in UT-SCC-20A cultures, but no effect was observed in the UT-SCC-24A cell line. Apoptosis, measured as enhanced caspase-3 activity, was induced by an agonistic Fas antibody (CH11) after cisplatin treatment in UT-SCC-24A cells.


CONCLUSIONS
Low-dose cisplatin treatment enhanced Fas expression in both cell lines and increased susceptibility to apoptosis in one of them.
Sundelin
Kaarina
K
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Linköping, Sweden. kaasu@inr.liu.se
Roberg
Karin
K
Grénman
Reidar
R
Håkansson
Leif
L
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology; D066246:ErbB Receptors / Q000096:biosynthesis; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016898:Interferon-alpha / Q000494:pharmacology; D015474:Isotretinoin / Q000494:pharmacology; D009062:Mouth Neoplasms / Q000378:metabolism*; D019014:fas Receptor / Q000096:biosynthesis
D000970:Antineoplastic Agents; D007155:Immunologic Factors; D016898:Interferon-alpha; D019014:fas Receptor; D018799:Intercellular Adhesion Molecule-1; D066246:ErbB Receptors; D015474:Isotretinoin; D002945:Cisplatin