ALTERED MONOCYTE CHEMOTACTIC AND ACTIVATING FACTOR GENE-EXPRESSION INHUMAN GLIOBLASTOMA CELL-LINES INCREASED THEIR SUSCEPTIBILITY TO CYTOTOXICITY

A cDNA encoding for human monocyte chemotactic and activating factor ( MCAF) was ligated into the retroviral vector pLXSN. These pMCAF-LXSN a nd antisense p-antiMCAF-LXSN vectors were transfected into HBT20 and H BT28 human brain tumor cells. HBT28 cells constitutively express high amounts of MCAF, whereas HBT20 cells express much less MCAF. HBT20 cel ls transfected with pMCAF-LXSN (HBT20-MCAF) showed significantly highe r MCAF mRNA expression and MCAF protein production than the HBT20-pare nt of HBT20 cells transfected with control vector (HBT20-LXSN). In con trast, supernatant from HBT28 cells transfected with p-antiMCAF-LXSN ( HBT28-antiMCAF) contained less MCAF than HBT28-parent, HBT20-LXSN, and HBT20 cells. Activated human monocyte killed HBT20-antiMCAF cells (P< 0.02), whereas HBT28-antiMCAF cells were killed more efficiently by ac tivated monocytes compared with HBT28-parent, HBT28-LXSN, and HBT28-MC AF cells (P<0.05). Cultured supernatants from activated monocytes plus HBT28-antiMCAF cells inhibited the growth of HBT20 and HBT28 cells, r espectively. Altered MCAF expression can therefore enhance the ability of activated monocytes to kill brain tumor cells. This increased cyto toxicity is partially dependent upon the basal state of MCAF in the in dividual tumor cells.