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 (TNF alpha) 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 TNF alpha, IL-13, or other activating signals are released in the tumour micro-environment and regulate the expression of VCAM-1 in malignant mesothelioma cells.
Ruco
L P
LP
Dipartimento di Medicina Sperimentale e Patologia, Università La Supienza, Roma, Italy.
de Laat
P A
PA
Matteucci
C
C
Bernasconi
S
S
Sciacca
F M
FM
van der Kwast
T H
TH
Hoogsteden
H C
HC
Uccini
S
S
Mantovani
A
A
Versnel
M A
MA
D015152:Blotting, Northern; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D018793:Interleukin-13 / Q000494:pharmacology; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
D018793:Interleukin-13; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1