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-re ceptor for the beta 2-integrins, LFA-1 and Mac-1, which are expressed on le ukocytes. 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 (N HOK), human papilloma virus (HPV)-immortalized human oral keratinocyte line s (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 demonstrate d 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 n ot fully account for the increased accumulation of ICAM-1 mRNA. Adhesion of peripheral blood mononuclear cells (PBMC) to epithelial cells correlated w ith cell surface ICAM-1 expression levels. This adhesion was inhibited by a ntibodies 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 l evels or with adhesion. Nonetheless, within each cell line, blocking of ICA M-1 or LFA-1/Mac-1 reduced LAK cell killing, suggesting that ICAM-1 is invo lved in mediating this killing.