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Intercellular adhesion molecule-1 release from human hepatocellular carcinoma
1Department of Internal Medicine, National Shikoku Cancer Center Hospital, Ehime, Japan.
Insights
Serum levels of adhesion molecules like E-selectin, VCAM-1, and ICAM-1 are elevated in liver disease patients. In hepatocellular carcinoma, elevated ICAM-1 is linked to tumor shedding, not just inflammation.
Area of Science:
- Immunology
- Hepatology
- Oncology
Background:
- Circulating adhesion molecules, including E-selectin, VCAM-1, and ICAM-1, play roles in inflammatory and cellular processes.
- Elevated levels of these molecules have been observed in various liver diseases, but their specific contributions in hepatocellular carcinoma (HCC) require further elucidation.
Purpose of the Study:
- To investigate and compare serum levels of E-selectin, VCAM-1, and ICAM-1 in patients with chronic hepatitis (CH), liver cirrhosis (LC), and HCC.
- To determine the relationship between these adhesion molecules and disease severity, particularly in HCC, and to assess the contribution of tumor shedding to circulating ICAM-1 levels.
Main Methods:
- Enzyme-linked immunosorbent assays (ELISA) were used to quantify serum levels of E-selectin, VCAM-1, and ICAM-1 in 38 CH, 29 LC, and 43 HCC patients, compared to 40 healthy controls.
- Immunohistochemistry was employed to evaluate the in situ expression of these adhesion molecules in 10 HCC tissue samples.
- Statistical analyses were performed to assess correlations between adhesion molecule levels, disease status, and tumor characteristics.
Main Results:
- All patient groups (CH, LC, HCC) exhibited significantly higher serum levels of E-selectin, VCAM-1, and ICAM-1 compared to normal controls.
- Serum VCAM-1 and ICAM-1 levels were correlated in CH and LC patients, but this correlation diminished in HCC patients, especially with larger tumors.
- While actual serum ICAM-1 levels did not correlate with tumor size, predicted ICAM-1 shedding from tumor cells showed a strong correlation with tumor size in HCC patients.
- Immunohistochemistry revealed enhanced ICAM-1 expression on HCC tumor cells, with no significant expression of E-selectin or VCAM-1.
Conclusions:
- Elevated serum adhesion molecules in HCC patients are primarily driven by underlying liver inflammation, similar to CH and LC.
- Tumor cells in HCC contribute to elevated serum ICAM-1 levels through shedding, and this shedding is proportional to tumor size.
- While inflammation is the main driver, tumor-derived ICAM-1 shedding represents a specific biomarker for HCC progression.
Abstract:
Serum levels of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were measured in 38 patients with chronic hepatitis (CH), 29 with liver cirrhosis (LC), and 43 with hepatocellular carcinoma (HCC) using enzyme-linked immunosorbent assays. All the patients showed significantly higher serum levels of these circulating adhesion molecules than 40 normal controls. The serum E-selectin level showed no relationship to the levels of the other adhesion molecules. Serum VCAM-1 levels were well correlated with serum 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 patients with large tumors (100 cm2) showed relatively high ICAM-1 levels. The amount of ICAM-1 shed from the tumor cells was calculated in the HCC patients as follows: actual serum ICAM-1 level minus basal ICAM-1 level released from the noncancerous liver (obtained from the regression 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 tumor size in HCC patients, the predicted ICAM-1 shedding was closely correlated with tumor size. When in situ expression of these adhesion molecules 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 levels of adhesion molecules in HCC patients are mainly attributable to the associated liver inflammation, although some ICAM-1 is shed into the circulation by tumor cells.