title: Regulated chemokine gene expression in mouse mesothelioma and mesothelial             cells: TNF-α upregulates both CC and CXC chemokine genes.
abstract: Many cancers express an array of chemokines which have the capacity to modulate             the nature and function of intratumoural leukocyte infiltrates. In malignant mesothelioma             (MM) neither the chemokine signalling networks nor their regulation have been             investigated despite the prominence of leucocytic infiltrates in both clinical             and experimental tumours. In this study, we examined constitutive and cytokine-regulated             expression of CC and CXC chemokine genes in mesothelioma and mesothelial cell             cultures derived from two different mouse strains (BALB/C and CBA/CaH). In mouse             MM and mesothelial cells MCP-1/JE, GRO-α/KC and RANTES were expressed whereas             MIP-1α and MIP-2 were infrequently expressed. Comparison of basal chemokine expression             showed that GRO-α/KC mRNA was overexpressed in the malignant cells whereas MCP-1             gene expression and release was downregulated. Treatment of mesothelioma cells             with IL-4, IFN-γ or TNF-α revealed that chemokine genes could be more responsive             to cytokines in the malignant compared to their mesothelial cells. TNF-α was consistently             the most potent positive regulator of both CC and CXC chemokine expression and             MCP-1 release. The present study for the first time provides a mechanistic insight             into the differential regulation of chemokine expression in malignant mesothelioma             cells and has implications for mesothelial chemokine signalling in mouse models.
authors.affiliation: Molecular Pharmacology Laboratory, School of Pharmacy, Western Australian Biomedical Research Institute and Curtin Health Innovation Research Institute, School of Pharmacy, Curtin University, Bentley, WA 6102, Australia. s.fox@curtin.edu.au
authors.forename: Simon A
authors.initials: SA
authors.lastname: Fox
authors.forename: Suzanne S
authors.initials: SS
authors.lastname: Loh
authors.forename: Sathish K
authors.initials: SK
authors.lastname: Mahendran
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Garlepp
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008654:Mesothelioma / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019742:Chemokines, CC; D019743:Chemokines, CXC; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha