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 (ECM) and ECM-bound cytokines modulate the expression of cell-surface molecules on target malignant cells, which may lead to changes in their susceptibility to cytolysis, in their ability to present antigens, and in the induction of local immune-cell activation and patrol. Eventually, these alterations 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 (IFNgamma) and tumor necrosis factor alpha (TNFalpha) on the surface expression 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 significantly changed either by naive ECM and its components or by ECM-bound cytokines. ECM synergized with IFNgamma and TNFalpha in inducing HLA-DR molecules on nonmalignant and malignant thyrocytes, with higher HLA-DR levels on the malignant cells. The laminin component, in particular, synergized with IFNgamma. Basal ICAM-1 expression on nonneoplastic cells was not significantly affected by the cytokines when grown in the absence of ECM, but was significantly upregulated when cells were cultured on ECM. In contrast, in malignant thyrocyte cultures, ECM significantly attenuated IFNgamma- and TNFalpha-mediated enhancement of ICAM-1 expression. We concluded that signals 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.
Miller
A
A
Immunology Research Units, Lady Davis Carmel Medical Center, Haifa, Israel.
Kraiem
Z
Z
Sobel
E
E
Lider
O
O
Lahat
N
N
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003315:Cornea / Q000166:cytology; D004357:Drug Synergism; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D007797:Laminin / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology; D013964:Thyroid Neoplasms; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000954:Antigens, Surface; D000970:Antineoplastic Agents; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D007797:Laminin; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma