SOLUBLE INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) IS RELEASED INTO THE SERUM AND ASCITES OF HUMAN OVARIAN-CARCINOMA PATIENTS AND IN NUDE-MICE BEARING TUMOR XENOGRAFTS

We have demonstrated that patients with ovarian carcinoma have higher levels of soluble intercellular adhesion molecule-1 (ICAM-1) in their serum and ascitic fluids than serum from normal individuals and non-ne oplastic gynaecological disease or ascites from patients with cirrhosi s. In order to investigate the source of the ICAM-1, and to study the mechanisms which regulate ICAM-1 relase in ovarian carcinoma, we have employed the nude mouse model system. Three different human ovarian ca rcinoma (HOC) cell lines were grown as ascitic tumours in the peritone al cavity of nude mice. HOC xenografts harvested from nude mice expres sed comparable levels of ICAM-1 on their cell surface. Human ICAM-1 wa s detected, with a species-specific ELISA, in serum and ascitic fluid of tumour-bearing mice, confirming that the tumours were the source of the ICAM-1. The three HOC xenografts showed different levels of ICAM- 1 release, but within each xenograft model the level of ICAM-1 in seru m and ascitic fluid correlated with the tumour burden. The level of IC AM-1 released by the HOC xenografts could be increased by in vivo trea tment with interferon gamma (IFN gamma). Interleukin 1 (IL-1), tumour necrosis factor (TNF) and IFN gamma increased the cell surface express ion of ICAM-1 and caused the release of soluble ICAM-1 from HOC cells established in vitro. The nude mouse provides a useful system in which to study the effects of modulating ICAM-1 release on the progression of ovarian carcinoma and suggests that measuring ICAM-1 levels in the blood or ascites of patients may provide an indication of tumour burde n.