DEFECTIVE EXPRESSION OF ADHESION MOLECULES ON HUMAN BLADDER-TUMOR ANDHUMAN TUMOR-CELL LINES

The pattern of expression of cell adhesion molecules, i.e., leucocyte function associated antigen 3 (LFA-3) and intercellular adhesion molec ule I (ICAM-1) on human bladder tumour biopsy specimens was investigat ed. Attempts were also made to study the pattern of induction of these molecules by established human cell lines in response to cytokines. T he results indicated that 15 of 25 tumour biopsy specimens were negati ve for ICAM-1, and amongst the remaining 10, only 1 showed strong posi tivity, whilst LFA-3 was expressed in 21 of 23 cases. Unlike LFA-3, th e pattern of ICAM-1 expression on established tumour cell lines was di fferent in that there were 7 of 21 cases showing positive staining. Th e parallel investigation of ICAM-1 and major histocompatibility comple x class II antigen expression on bladder tumours showed that in II of 18 cases, there was a concomitant expression or complete absence of th ese molecules. In the remaining 7, there were 6 cases where only class II expression was observed. Exposure of cell lines to interferons alp ha or gamma had no effects on LFA-3 expression. In contrast, interfero n gamma induced ICAM-1 on all the eight lines with constitutive ICAM-1 expression, whereas interferon alpha upregulated only 2 of these 8 li nes. The mean +/- SD values for ICAM-1 expression on the eight inducib le lines were 617 +/- 406 cpm before and 943 +/- 471 cpm (p = 0.001) a fter interferon gamma stimulation. The pattern of ICAM-1 inducibility of a bladder cell line Fen to interferon remained unchanged following transfection of a beta(2)-microglobulin gene and correction of cell su rface HLA class I antigens. These results indicate that there was a si gnificant minority of bladder tumours and tumour cell lines with abnor mal cell adhesion molecule expression. In some cases, the abnormality in cell lines could not be corrected by cytokine stimulation. It is po ssible that these abnormalities may play a critical role in the overal l tumour strategy for escape from immunological detection.