SUPPRESSION OF TUMOR-GROWTH AND METASTASIS OF MURINE RENAL ADENOCARCINOMA BY SYNGENEIC FIBROBLASTS GENETICALLY-ENGINEERED TO SECRETE THE JEMCP-1 CYTOKINE/

The murine monocyte chemoattractant protein 1, JE/MCP-1, like its huma n counterpart monocyte chemotactic and activating factor (MCAF), attra cts monocytes-macrophages to tumor tissues, In previous studies we rep orted that expression of the JE/MCP-1 gene in murine colon carcinoma c ells reduced their tumorigenicity and suppressed their metastatic pote ntial, We now demonstrate that the growth and metastasis of the renal adenocarcinoma cell line RENCA are reduced when it was admired with sy ngeneic fibroblasts engineered to secrete the JE/MCP-1 cytokine before injection. Culture supernatants of JE/MCP-1-expressing cells plus lip opolysaccharide (LPS) synergistically activated tumoricidal properties in syngeneic macrophages against RENCA cells, This activity was block ed by anti-JE/MCP-1 antibody, indicating that JE/MCP-1 was involved in priming the macrophages to respond to LPS, Moreover, alveolar macroph ages isolated shortly after iv injections of JE/MCP-1-transfected cell s were cytotoxic to RENCA cells in vitro, Collectively, these data sug gest that in addition to its chemotactic properties, JE/MCP-1 can syne rgize with bacterial endotoxins to activate macrophages, thus providin g a rationale for the use of the JE/MCP-1 protein as a modality for tr eatment of metastasis.