PMID- 10679114 OWN - NLM STAT- MEDLINE DCOM- 20000323 LR - 20190515 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 164 IP - 5 DP - 2000 Mar 1 TI - Induction of chemokine secretion and enhancement of contact-dependent macrophage cytotoxicity by engineered expression of granulocyte-macrophage colony-stimulating factor in human colon cancer cells. PG - 2728-37 AB - We investigated the role of tumor cell-derived GM-CSF in recruitment and tumoricidal activation of tissue macrophages. Transfection of the murine GM-CSF gene into KM12SM human colon cancer cells decreased the tumorigenicity of transfected cells and nontransfected bystander colon cancer cells in nude mice. Sequential tissue sections from sites injected with high GM-CSF-producing tumor cells (but not from nontransfected or low GM-CSF-producing cells) demonstrated a dense infiltration of polymorphonuclear cells (PMN), followed by infiltration of macrophages, which correlated with expression of the macrophage-inflammatory protein-1alpha and the monocyte chemoattractant protein-1 (MCP-1) in mouse PMN and macrophages. GM-CSF-producing KM12SM cells were highly sensitive to lysis by mouse macrophages and also increased macrophage-mediated lysis of bystander nontransfected KM12SM cells. The incubation of macrophages with GM-CSF induced expression of the CD11b surface adhesion molecule, which was associated with increased attachment to tumor cells. All KM12SM cells were sensitive to macrophage-mediated lysis in the presence of rGM-CSF and recombinant MCP-1. Collectively, the results demonstrate that tumor cell-derived GM-CSF stimulates PMN and macrophages to secrete macrophage-inflammatory protein-1alpha and MCP-1, which triggers recruitment of mononuclear cells, induces expression of adhesion molecules on macrophages, and enhances contact-dependent cytolysis of tumor cells. FAU - Shinohara, H AU - Shinohara H AD - Department of Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. FAU - Yano, S AU - Yano S FAU - Bucana, C D AU - Bucana CD FAU - Fidler, I J AU - Fidler IJ LA - eng GR - CA16672/CA/NCI NIH HHS/United States GR - R35-CA42107/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL4) RN - 0 (Chemokines) RN - 0 (Macrophage Inflammatory Proteins) RN - 0 (Macrophage-1 Antigen) RN - 0 (Recombinant Proteins) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - Cell Communication/genetics/*immunology MH - Cell Movement/genetics/immunology MH - Chemokine CCL2/biosynthesis/genetics/metabolism MH - Chemokine CCL4 MH - Chemokines/biosynthesis/genetics/*metabolism MH - Coculture Techniques MH - Colonic Neoplasms/genetics/*immunology/*metabolism/prevention & control MH - Cytotoxicity, Immunologic/genetics/*immunology MH - Gene Expression Regulation, Neoplastic/immunology MH - Granulocyte-Macrophage Colony-Stimulating Factor/*biosynthesis/genetics/*immunology/pharmacology MH - HT29 Cells MH - Humans MH - Injections, Subcutaneous MH - Macrophage Inflammatory Proteins/biosynthesis/genetics MH - Macrophage-1 Antigen/biosynthesis MH - Macrophages/*immunology/metabolism MH - Male MH - Mice MH - Mice, Nude MH - Neoplasm Transplantation MH - Neutrophils/immunology MH - Protein Engineering MH - Recombinant Proteins MH - Transfection MH - Tumor Cells, Cultured EDAT- 2000/02/29 09:00 MHDA- 2000/03/25 09:00 CRDT- 2000/02/29 09:00 PHST- 2000/02/29 09:00 [pubmed] PHST- 2000/03/25 09:00 [medline] PHST- 2000/02/29 09:00 [entrez] AID - ji_v164n5p2728 [pii] AID - 10.4049/jimmunol.164.5.2728 [doi] PST - ppublish SO - J Immunol. 2000 Mar 1;164(5):2728-37. doi: 10.4049/jimmunol.164.5.2728.