Extracellular Matrix of Glioblastoma Inhibits Polarization and Transmigration of T Cells: The Role of Tenascin-C in Immune Suppression
| Autor: | Bei Chang Yang, Chung Chen Su, Yu Ping Lin, Yu Jung Cheng, Rudy L. Juliano, Huan Ching Lin, Jyun Yuan Huang |
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| Rok vydání: | 2010 |
| Předmět: |
T cell
Immunology Jurkat cells Jurkat Cells Interleukin 21 Cell Movement T-Lymphocyte Subsets Cell Line Tumor Immune Tolerance medicine Humans Immunology and Allergy Cytotoxic T cell Extracellular Signal-Regulated MAP Kinases Antigen-presenting cell Cells Cultured Interleukin 3 Microscopy Confocal CD40 biology Cell Polarity Tenascin Hep G2 Cells Extracellular Matrix Cell biology Enzyme Activation Gene Expression Regulation Neoplastic medicine.anatomical_structure Cell Migration Inhibition biology.protein Interleukin 12 Glioblastoma |
| Zdroj: | The Journal of Immunology. 185:1450-1459 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0901352 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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