van Duinen C M, van den Broek L J, Vermeer B J, Fleuren G J, Bruijn J A
Department of Pathology, University of Leiden, The Netherlands.
Cancer. 1994 Apr 15;73(8):2131-9. doi: 10.1002/1097-0142(19940415)73:8<2131::aid-cncr2820730818>3.0.co;2-1.
The process of multistep tumor development has been studied thoroughly in the development of malignant melanomas. The authors investigated the expression of cellular adhesion molecules in nevomelanocytic lesions to explore a postulated role of adhesion molecules in cell-cell and cell-matrix interactions during tumor development.
Sections of 20 nevocellular nevi, 35 dysplastic nevi, 6 melanomas in situ, and 20 malignant melanomas were investigated with respect to their expression of intercellular adhesion molecule-1 (ICAM-1), inducible cell adhesion molecule-110 (INCAM-110)/vascular cell adhesion molecule-1 (VCAM-1), E-selectin, lymphocyte function-associated antigen-1 (LFA-1), and the integrins for very late antigen-(VLA) alpha-(alpha) 2 and VLA-alpha 6; for these studies, monoclonal antibodies were used and indirect immunoperoxidase and immunofluorescence staining methods were performed.
In the transformation from benign to malignant neoplasms, the expression of ICAM-1 was upregulated strongly. The expression of VLA-alpha 2 on tumor cells increased whereas that of VLA-alpha 6 decreased; these alterations corresponded to changes previously observed in their ligands within the extracellular matrix. These results were statistically significant. In addition, ICAM-1, INCAM-110/VCAM-1, and E-selectin were detected in activated endothelial cells, probably as a result of cytokine activation. The ligand for ICAM-1, LFA-1, was confined to mononuclear cells.
The increase in ICAM-1 and VLA-alpha 2 expression and the decrease of VLA-alpha 6 expression may, in combination with specific matrix alterations, lead to a change in cell-cell and cell-matrix interaction, thereby contributing to the invasive property of melanocytic tumor cells. The neoexpression of INCAM-110/VCAM-1 and E-selectin in pigmented skin lesions may play a role in both infiltrative growth and the generation of a host reaction toward these tumors.
