Relationship of the interleukin-1 system with neuroendocrine and exocrine markers in human colon cancer cell lines

Interleukin 1 (IL-1) is known to regulate the proliferation and differentiation of normal and malignant immune cells as well as other cell types. Expression of IL-1 (alpha and beta), IL-1 receptors (RI and RII) and IL-1 receptor antagonist (IL-1RA) was determined by RT-PCR in seven human colon carcinoma cell lines (COLO 320DM, LoVo, SW403, SW1116, SW1417, LS123 and LS174t). Influence of IL-1 on the secretion of the neuroendocrine (NE) differentiation marker chromogranin A (CGA) and the exocrine marker carcinoembryonic antigen (CEA) was examined by Western blotting. Our data indicate that CGA and IL-1RI are expressed by all seven, IL-1 beta by five, IL-1RII and IL-1RA by six lines. IL-1 alpha transcripts were found only in three lines (LoVo, SW1116 and LS174t) and correlated with high CEA levels and aggressive growth behavior. "Pure" NE cell lines (COLO 320DM and LS123) secreted the highest levels of CGA, but the lowest levels of CEA and were IL-1 (alpha and beta) negative. Exogenously added IL-1 caused a decrease in CGA, but an increase in CEA secretion. Our results suggest an inverse relationship between IL-1 and NE differentiation, as well as a direct relationship between IL-1 and CEA expression in colon carcinoma. (C) 2002 Elsevier Science Ltd. All rights reserved.