title: A forward loop between glioma and microglia: glioma-derived extracellular matrix-activated microglia secrete IL-18 to enhance the migration of glioma cells.
abstract: The mediators and cellular effectors of inflammation are important constituents of the local environment of tumors. In some occasions, oncogenic changes induce an inflammatory microenvironment that promotes the progression of tumors. In gliomas, the presence of microglia may represent tumor-related inflammation and microglia activation, and subsequent inflammatory responses may influence tumor growth and metastasis. Here, we found that C6 glioma--but not primary astrocyte-derived extracellular matrix (ECM) could activate microglia, including primary microglia and BV-2 cell line, and activated microglia-secreted interleukin (IL)-18, a potent inflammatory cytokine of the IL-1 family, to promote C6 migration. In addition, by coating purified ECM components, it was found that secretion of IL-18 by activated microglia was enhanced when microglia encountered with fibronectin and vitronectin. Furthermore, IL-18-induced C6 migration and microfilament disassembly were antagonized by iNOS inhibitor, guanylate cyclase inhibitor, and protein kinase G inhibitor. Taken together, these results indicate that IL-18 secreted by microglia, which was activated by C6 glioma-derived ECM, enhanced migration of C6 glioma through NO/cGMP pathway.
authors: Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Wei-Lan
authors: WL
authors: Yeh
authors: Dah-Yuu
authors: DY
authors: Lu
authors: Houng-Chi
authors: HC
authors: Liou
authors: Wen-Mei
authors: WM
authors: Fu
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D005910:Glioma / Q000378:metabolism*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D019096:Vitronectin / Q000494:pharmacology
chemical_list: D005353:Fibronectins; D020382:Interleukin-18; D019096:Vitronectin; D009569:Nitric Oxide; D006152:Cyclic GMP