title: Different progression of tumor xenografts between mucin-producing and mucin-non-producing mammary adenocarcinoma-bearing mice.
abstract: Previously, we found that MUC2 mucins could activate monocytes/macrophages through a scavenger receptor leading to cyclooxygenase (COX) 2 induction and overproduction of prostaglandin E2 (PGE2). To investigate the role of mucins in the tumor-bearing state, we compared s.c. tumor formation by using mucin-producing (TA3-Ha) and mucin-non-producing (TA3-St) cloned variants of mouse mammary adenocarcinomas. Expression of COX2 mRNA and protein and production of PGE2 were elevated in peritoneal macrophages stimulated with epiglycanin, which is a mucin-like glycoprotein produced by TA3-Ha cells. S.c. tumor tissues comprising TA3-Ha cells grew much faster than tissues comprising TA3-St cells. COX2 protein and vascular endothelial growth factor in TA3-Ha tumor tissues were elevated compared with the TA3-St tumor tissues. Although similar numbers of macrophages were observed immunochemically in the two types of tumor tissues, COX2 was induced prominently in the infiltrating macrophages in TA3-Ha tumor tissues but only faintly in TA3-St tumor tissues. Furthermore, angiogenesis progressed remarkably in TA3-Ha tumor tissues but only slightly in TA3-St tumor tissues. Epiglycanin-induced overproduction of PGE2 down-regulated interleukin-12 production by macrophages. IFN-gamma-producing CD4 T cells in spleens obtained from TA3-Ha tumor-bearing mice were significantly reduced compared with TA3-St tumor-bearing mice, suggesting that mucins cause PGE2-mediated immune suppression. Actually, the tumor growth of a TA3-Ha cell xenograft was suppressed effectively by oral administration of a COX2 inhibitor but that of a TA3-St cell one was not. These results suggest that mucins play an important role in tumor progression through overproduction of PGE2.
authors.affiliation: Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Kyoto, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Sugihara
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yoshida
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Shigenobu
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takagi
authors.forename: Koji
authors.initials: K
authors.lastname: Maruyama
authors.forename: Noriko
authors.initials: N
authors.lastname: Takeuchi
authors.forename: Munetoyo
authors.initials: M
authors.lastname: Toda
authors.forename: Mizue
authors.initials: M
authors.lastname: Inoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakada
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis; D018450:Disease Progression; D004790:Enzyme Induction; D017308:Etodolac / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000494:pharmacology; D051379:Mice; D008805:Mice, Inbred A; D009077:Mucins / Q000096:biosynthesis*; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D008562:Membrane Glycoproteins; D009077:Mucins; C016424:epiglycanin protein, mouse; D017308:Etodolac; D051546:Cyclooxygenase 2; D015232:Dinoprostone