Extracellular matrix of glioblastoma inhibits polarization and transmigration of T cells: the role of tenascin-C in immune suppression.
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.
Huang
Jyun-Yuan
JY
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
Cheng
Yu-Jung
YJ
Lin
Yu-Ping
YP
Lin
Huan-Ching
HC
Su
Chung-Chen
CC
Juliano
Rudy
R
Yang
Bei-Chang
BC
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*
D019063:Tenascin; D048049:Extracellular Signal-Regulated MAP Kinases