Modulation of human leukocyte antigen and intracellular adhesion molecule-1 surface expression in malignant and nonmalignant human thyroid cells by cytokines in the context of extracellular matrix

Interactions between malignant cells and their environment are achieved via cell-surface receptors and adhesion molecules. The extracellular matrix (E CM) and ECM-bound cytokines modulate the expression of cell-surface molecul es on target malignant cells, which may lead to changes in their susceptibi lity to cytolysis, in their ability to present antigens, and in the inducti on of local immune-cell activation and patrol. Eventually, these alteration s may culminate in either the destruction, or escape and proliferation, of the tumor. We studied the effects of the ECM and its components in a "naive " form or following binding of the inflammatory cytokines interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha) on the surface expr ession of human leukocyte antigen (HLA) class-I, HLA class-II (HLA-DR), and intracellular adhesion molecule-1 (ICAM-1), on nonmalignant and malignant thyroid cells. The basal expression of HLA class-I molecules was not signif icantly changed either by naive ECM and its components or by ECM-bound cyto kines. ECM synergized with IFN gamma and TNF alpha in inducing HLA-DR molec ules on nonmalignant and malignant thyrocytes, with higher HLA-DR levels on the malignant cells. The laminin component, in particular, synergized with IFN gamma. Basal ICAM-1 expression on nonneoplastic cells was not signific antly affected by the cytokines when grown in the absence of ECM, but was s ignificantly upregulated when cells were cultured on ECM. In contrast, in m alignant thyrocyte cultures, ECM significantly attenuated IFN gamma- and TN F alpha -mediated enhancement of ICAM-1 expression. We concluded that signa ls derived from ECM-embedded cytokines participate in the regulation of key thyroid cell surface molecules and, thus, may affect the final outcome of human thyroid malignancies.