AUTOCRINE REGULATION OF ICAM-1 EXPRESSION ON BLADDER-CANCER CELL-LINES - EVIDENCE FOR THE ROLE OF IL-1-ALPHA

We have studied the autocrine regulation of essential expression of the intercellular adhesion molecule-1 (ICAM-1) on 8 transitional cell carcinoma (TCC) cell lines (histopathological grades 1-3). The constitutive expression of ICAM-1 was regulated by soluble factors in an autocrine fashion. These factors were produced by all cell lines, with the exception of the MGH-U1 cell line. The effects observed could be largely attributed to IL-1 alpha. However, the residual ICAM-1 inducing activity (up to 30% of ICAM-1 induction) could not be associated with any known ICAM-1 inducers (IFN gamma, TNF alpha, TNF beta, IL-1 alpha, IL-1 beta, IL-4, retinoic acid, LPS). In contrast to recombinant derived cytokines, the IL-alpha present in tissue culture supernatant was only able to induce ICAM-1 on high-grade tumours and not low-grade cells. This discriminative effect is similar to that noted following in vitro culture of tumour cells with bacillus Calmette-Guerin organisms. Whether the production of soluble factors (e.g., IL-1 alpha) by TCC cell lines plays an essential autocrine role for bladder tumours and/or affects the interaction with cells of the immune system needs to be investigated further.