title: Extracellular matrix of glioblastoma inhibits polarization and transmigration of T cells: the role of tenascin-C in immune suppression.
abstract: Dense accumulations of T cells are often found in peritumoral areas, which reduce the efficiency of contact-dependent lysis of tumor cells. We demonstrate in this study that the extracellular matrix (ECM) produced by tumors can directly regulate T cell migration. The transmigration rate of several T cells including peripheral blood primary T cell, Jurkat, and Molt-4 measured for glioma cells or glioma ECM was consistently low. Jurkat cells showed reduced amoeba-like shape formation and delayed ERK activation when they were in contact with monolayers or ECM of glioma cells as compared with those in contact with HepG2 and MCF-7 cells. Phospho-ERK was located at the leading edge of migrating Jurkat cells. Glioma cells, but not MCF-7 and HepG2 cells, expressed tenascin-C. Knocking down the tenascin-C gene using the short hairpin RNA strategy converted glioma cells to a transmigration-permissive phenotype for Jurkat cells regarding ERK activation, transmigration, and amoeba-like shape formation. In addition, exogenous tenascin-C protein reduced the amoeba-like shape formation and transmigration of Jurkat cells through MCF-7 and HepG2 cell monolayers. A high level of tenascin-C was visualized immunohistochemically in glioma tumor tissues. CD3(+) T cells were detected in the boundary tumor area and stained strongly positive for tenascin-C. In summary, glioma cells can actively paralyze T cell migration by the expression of tenascin-C, representing a novel immune suppressive mechanism achieved through tumor ECM.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jyun-Yuan
authors.initials: JY
authors.lastname: Huang
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Cheng
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Lin
authors.forename: Huan-Ching
authors.initials: HC
authors.lastname: Lin
authors.forename: Chung-Chen
authors.initials: CC
authors.lastname: Su
authors.forename: Rudy
authors.initials: R
authors.lastname: Juliano
authors.forename: Bei-Chang
authors.initials: BC
authors.lastname: Yang
mesh_terms: D045744:Cell Line, Tumor; D002464:Cell Migration Inhibition / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D005109:Extracellular Matrix / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D005909:Glioblastoma / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D056945:Hep G2 Cells; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D019169:Jurkat Cells; D018613:Microscopy, Confocal; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D019063:Tenascin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D019063:Tenascin; D048049:Extracellular Signal-Regulated MAP Kinases