DIFFERENTIAL-EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA ON PROLIFERATION, CELL-SURFACE ANTIGEN EXPRESSION, AND CYTOKINE INTERACTIONS IN MALIGNANT GLIOMAS

TUMOR NECROSIS FACTOR-alpha (TNF-alpha), a cytokine produced by astrocytes in vivo and in vitro, was tested for its effects on two malignant astrocytoma cell lines (A-172, U-87). Both lines were immunoreactive for glial fibrillary acidic protein, vimentin, Class I antigens, and interleukin-6. The lines differed in their expression of Class II and intercellular adhesion molecule-1 (ICAM-1) antigenic determinants: A-172 cells were negative for both Class II and ICAM-1 antigens, while U-87 cells were intensely positive for Class II and weakly positive for ICAM-1. When these astrocytoma cell lines were exposed to TNF-alpha, A-172 growth was stimulated while U-87 growth was inhibited. Furthermore, in U-87 cells, TNF-alpha enhanced both ICAM-1 and interleukin-1beta (IL-1beta) expression, and decreased immunoreactivity for transforming growth factor-beta (TGF-beta) protein. In contrast, in the presence of TNF-alpha, A-172 cells remained negative for IL-1beta and TGF-beta, but showed an increased expression of ICAM-1. These results demonstrate that TNF-alpha can induce changes in growth rate, cytokine production, and surface antigen expression in malignant astrocytomas; however, the nature of these changes is dependent on the specific characteristics of these malignant astrocytomas. The resultant variability in the immunological microenvironment of these tumors may reflect differences in their growth potential.