PMID- 10683275 OWN - NLM STAT- MEDLINE DCOM- 20000323 LR - 20220223 IS - 0014-4886 (Print) IS - 0014-4886 (Linking) VI - 161 IP - 1 DP - 2000 Jan TI - Experimental gliosarcoma induces chemokine receptor expression in rat brain. PG - 85-95 AB - Macrophage/microglial infiltration is a characteristic feature of brain tumors. The functional role(s) of these cells is complex and could include both trophic and suppressive effects on tumors. Information has recently emerged about the molecular signals that regulate the accumulation and function of monocytes in pathological disorders. Recent data indicate that the chemokine, monocyte chemoattractant protein-1 (MCP-1), a potent monocyte activating and chemotactic factor, is a primary regulator of the macrophage response in brain tumors. We hypothesized that if MCP-1 regulates macrophage/microglial infiltration, then expression of the specific MCP-1 receptor, CCR2, will be induced in peritumoral tissue and/or within brain tumors. Identification of a specific receptor that is preferentially expressed in brain tumors could be important both in terms of tumor biology and as a potential therapeutic target. We used an established experimental gliosarcoma model, induced by intracranial transplantation of cultured 9L cells into adult rat brain, to test this hypothesis. RT-PCR analysis showed high levels of both MCP-1 and CCR2 mRNA and Western blot analysis demonstrated increased CCR2 protein in tumor extracts. Immunocytochemistry showed CCR2 immunoreactive microglia in peritumoral tissue and, unexpectedly, that intrinsic tumor cells, rather than monocytes, were the predominant source of CCR2. These results demonstrate that CCR2 expression is markedly upregulated in this brain tumor model. CI - Copyright 2000 Academic Press. FAU - Galasso, J M AU - Galasso JM AD - Neuroscience Program, University of Michigan, Ann Arbor, Michigan, 48109-0646, USA. FAU - Stegman, L D AU - Stegman LD FAU - Blaivas, M AU - Blaivas M FAU - Harrison, J K AU - Harrison JK FAU - Ross, B D AU - Ross BD FAU - Silverstein, F S AU - Silverstein FS LA - eng GR - NS31054/NS/NINDS NIH HHS/United States GR - NS35059/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Autoantigens) RN - 0 (Ccl2 protein, rat) RN - 0 (Ccr2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (DNA Primers) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Messenger) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) RN - 0 (Receptors, Cytokine) SB - IM MH - Animals MH - Autoantigens/analysis/*genetics MH - Blotting, Western MH - Brain Chemistry/genetics/immunology MH - Brain Neoplasms/diagnosis/*immunology/physiopathology MH - *Chemokine CCL2 MH - DNA Primers MH - Gene Expression Regulation, Neoplastic/drug effects MH - Gliosarcoma/diagnosis/*immunology/physiopathology MH - Lipopolysaccharides/pharmacology MH - Macrophages/immunology MH - Magnetic Resonance Imaging MH - Male MH - Microglia/physiology MH - Neoplasm Transplantation MH - RNA, Messenger/analysis MH - Rats MH - Rats, Inbred F344 MH - Receptors, CCR2 MH - *Receptors, Chemokine MH - Receptors, Cytokine/analysis/*genetics EDAT- 2000/02/23 09:00 MHDA- 2000/03/25 09:00 CRDT- 2000/02/23 09:00 PHST- 2000/02/23 09:00 [pubmed] PHST- 2000/03/25 09:00 [medline] PHST- 2000/02/23 09:00 [entrez] AID - S0014-4886(99)97249-7 [pii] AID - 10.1006/exnr.1999.7249 [doi] PST - ppublish SO - Exp Neurol. 2000 Jan;161(1):85-95. doi: 10.1006/exnr.1999.7249.