Extracellular matrix of glioblastoma inhibits polarization and transmigration of T cells: The role of tenascin-C in immune suppression

Jyun Yuan Huang, Yu Jung Cheng, Yu Ping Lin, Huan Ching Lin, Chung Chen Su, Rudy Juliano, Bei-Chang Yang

研究成果: Article

31 引文 斯高帕斯(Scopus)

摘要

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 transmigrationpermissive 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.

原文English
頁(從 - 到)1450-1459
頁數10
期刊Journal of Immunology
185
發行號3
DOIs
出版狀態Published - 2010 八月 1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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