Increased ICAM-1 expression in transformed human oral epithelial cells: molecular mechanism and functional role in peripheral blood mononuclear cell adhesion and lymphokine-activated-killer cell cytotoxicity.
The intercellular adhesion molecule-1 (ICAM-1, CD54) serves as a counter-receptor for the beta2-integrins, LFA-1 and Mac-1, which are expressed on leukocytes. Although expression of ICAM-1 on tumor cells has a role in tumor progression and development, information on ICAM-1 expression and its role in oral cancer has not been established. Normal human oral keratinocytes (NHOK), human papilloma virus (HPV)-immortalized human oral keratinocyte lines (HOK-16B, HOK-18A, and HOK-18C), and six human oral neoplastic cell lines (HOK-16B-BaP-T1, SCC-4, SCC-9, HEp-2, Tu-177 and 1483) were used to study ICAM-1 expression and its functional role in vitro. Our results demonstrated that NHOK express negligible levels of ICAM-1, whereas immortalized human oral keratinocytes and cancer cells express significantly higher levels of ICAM-1, except for HOK-16B-BaP-T1 and HEp-2. Altered mRNA half-lives did not fully account for the increased accumulation of ICAM-1 mRNA. Adhesion of peripheral blood mononuclear cells (PBMC) to epithelial cells correlated with cell surface ICAM-1 expression levels. This adhesion was inhibited by antibodies specific for either ICAM-1 or LFA-1/Mac-1, suggesting a role for these molecules in adhesion. In contrast, lymphokine-activated-killer (LAK) cell cytotoxic killing of epithelial cells did not correlate with ICAM-1 levels or with adhesion. Nonetheless, within each cell line, blocking of ICAM-1 or LFA-1/Mac-1 reduced LAK cell killing, suggesting that ICAM-1 is involved in mediating this killing.
Section of Endodontics, UCLA School of Dentistry, 90095-1668, USA. gtjhuang@ucla.edu
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D002448:Cell Adhesion; D002461:Cell Line, Transformed / Q000378:metabolism / Q000821:virology; D002472:Cell Transformation, Viral; D003602:Cytotoxicity, Immunologic; D015972:Gene Expression Regulation, Neoplastic; D006207:Half-Life; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000502:physiology; D009061:Mouth Mucosa / Q000473:pathology* / Q000821:virology; D009062:Mouth Neoplasms / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D027383:Papillomaviridae / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018799:Intercellular Adhesion Molecule-1