Cloning of DLM-1, a novel gene that is up-regulated in activated macrophages, using RNA differential display

Tumors interact with their environment, reprogramming host cells to induce responses such as angiogenesis, inflammation, immunity and immune suppressi on. To understand these processes, it is important to identify and isolate new genes whose expression is induced in host tissues in response to tumors . Ascites tumors offer an attractive model for isolating such genes, becaus e responding host peritoneal lining tissues can be cleanly separated from t umor cells growing in suspension within the peritoneal cavity. We here repo rt the cloning by differential display of a novel gene, DLM-1, that is high ly up-regulated in the peritoneal lining tissue of mice bearing MOT ascites tumors. Mouse peritoneal macrophages, stimulated by IFN-gamma or LPS, also expressed significant amounts of DLM-1. Up-regulation of DLM-1 became evid ent by 4 h after stimulation with IFN-gamma and was not blocked by cyclohex imide, suggesting the presence of IFN responding elements in its transcript ion regulation region. DLM-1 RNA was detected at significant levels in norm al mouse lung, intestinal epithelium, liver and thymus by Northern blot ana lysis. In situ hybridization of MOT and HT-29 mouse subcutaneous transplant ed solid tumors revealed strong DLM-1 expression in the host reactive strom al cells, but not the tumor cells. Sequence analysis of the full-length cDN A clone revealed that it encodes a protein of approx. M-r 44330 with multip le potential protein kinase C and casein kinase II phosphorylation sites. O ur data suggest that DLM-1 plays a role in such important processes as host response in neoplasia. (C) 1999 Elsevier Science B.V. All rights reserved.