EXPRESSION OF ICAM‐1 AND VCAM‐1 IN HUMAN MALIGNANT MESOTHELIOMA

Intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) are cytokine‐inducible adhesion molecules which recognize ligands that are highly expressed on leukocytes. Expression of ICAM‐1 and VCAM‐1 was investigated in tissue sections of 16 cases of malignant mesothelioma (seven epithelial, eight biphasic, and one sarcomatoid) using immunohistochemistry. Neoplastic cells were diffusely and intensely stained for ICAM‐1 in all cases. VCAM‐1 was detected in 14 of 16 cases. The percentage of VCAM‐1‐positive tumour cells was more than 50 per cent in eight cases and the staining was observed mainly in epithelial‐like cells. VCAM‐1 was rarely expressed in other malignant tumours of epithelial origin, being present in only 1 of 58 cases of carcinoma originating from different anatomical sites. At the cellular level, ICAM‐1 and VCAM‐1 appeared co‐distributed, the staining for both being cytoplasmic with a membrane reinforcement. The regulation of VCAM‐1 expression by neoplastic mesothelial cells was investigated in vitro using 14 mesothelioma cell lines. ICAM‐1 was expressed by cultured cells of all mesothelioma cell lines, even in the absence of cytokines. VCAM‐1 was detected in 10–50 per cent of the cells in three non‐stimulated mesothelioma cell lines (mero‐95, mero‐96, and mero‐134), and was absent or poorly expressed in the remaining 11. Exposure of a negative cell line (mero‐48a) to an optimal concentration of tumour necrosis factor alpha (TNFα) or interleukin‐13 (IL‐13) for 6–18 h resulted in the induction of VCAM‐1 mRNA synthesis and in VCAM‐1 expression at the membrane level in 60–70 per cent of the cells. These findings are consistent with the possibility that TNFα, IL‐13, or other activating signals are released in the tumour micro‐environment and regulate the expression of VCAM‐1 in malignant mesothelioma cells.