INTERCELLULAR-ADHESION MOLECULE-1 RELEASE FROM HUMAN HEPATOCELLULAR-CARCINOMA

Serum levels of E-selectin, vascular cell adhesion molecule-1 (VCAM-1) , and intercellular adhesion molecule-1 (ICAM-1) were measured in 38 p atients with chronic hepatitis (CH), 29 with liver cirrhosis (LC), and 43 with hepatocellular carcinoma (HCC) using enzyme-linked immunosorb ent assays. All the patients showed significantly higher serum levels of these circulating adhesion molecules than 40 normal controls. The s erum E-selectin level showed no relationship to the levels of the othe r adhesion molecules. Serum VCAM-1 levels were well correlated with se rum ICAM-1 levels in CH and LC patients. In HCC patients, however, the close correlation between VCAM-1 and ICAM-1 was lost, because the pat ients with large tumors (100 cm(2)) showed relatively high ICAM-1 leve ls. The amount of ICAM-1 shed from the tumor cells was calculated in t he HCC patients as follows: actual serum ICAM-1 level minus basal ICAM -1 level released from the noncancerous liver (obtained from the regre ssion line between ICAM-1 and VCAM-1 in CH and LC patients). Although there was no relationship between the actual ICAM-1 level and the tumo r size in HCC patients, the predicted ICAM-1 shedding was closely corr elated with tumor size. When in situ expression of these adhesion mole cules was evaluated in 10 HCC tissues using immunohistochemistry, the tumor cells exhibited enhanced ICAM-1 expression but did not express E -selectin and VCAM-1. These results suggest that the elevated serum le vels of adhesion molecules in HCC patients are mainly attributable to the associated liver inflammation, although some ICAM-1 is shed into t he circulation by tumor cells.