Suppression of tumor formation in vivo by expression of the JE gene in malignant cells.
The early growth response gene JE encodes a monocyte chemoattractant, MCP-1. The JE/MCP-1 protein attracts and stimulates human monocytes and induces monocyte-mediated inhibition of tumor cell growth in vitro. Expression of human or murine JE/MCP-1 in Chinese hamster ovary (CHO) cells completely suppressed their ability to form tumors in nude mice. Coinjection of JE/MCP-1-expressing cells with nonexpressing CHO cells or with HeLa cells also prevented tumor formation. Since JE/MCP-1 expression had no discernible effect on the tranformed phenotype of these cells in vitro, the suppressive effect depends on host animal factors. These factors are likely to be components of the inflammatory response, because JE/MCP-1-expressing cells elicited a predominantly monocytic infiltrate at the site of injection. Our results suggest that JE/MCP-1 protein may be useful in cancer therapy.
Rollins
B J
BJ
Division of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Sunday
M E
ME
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D014162:Transfection; D014183:Transplantation, Heterologous
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D008715:Methionine