Glioblastoma Inhibition by Cell Surface Immunoglobulin Protein EWI-2, In Vitro and In Vivo1,2
| Autor: | Kolesnikova, Tatiana V, Kazarov, Alexander R, Lemieux, Madeleine E, Lafleur, Marc A, Kesari, Santosh, Kung, Andrew L, Hemler, Martin E |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
Brain Immunoglobulins Membrane Proteins Mice Nude Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic Mice Antigens CD Astrocytes embryonic structures Tumor Cells Cultured Animals Humans Genes Tumor Suppressor Glioblastoma Research Article Cell Proliferation HeLa Cells Protein Binding |
| Popis: | EWI-2, a cell surface IgSF protein, is highly expressed in normal human brain but is considerably diminished in glioblastoma tumors and cell lines. Moreover, loss of EWI-2 expression correlated with a shorter survival time in human glioma patients, suggesting that EWI-2 might be a natural inhibitor of glioblastoma. In support of this idea, EWI-2 expression significantly impaired both ectopic and orthotopic tumor growth in nude mice in vivo. In vitro assays provided clues regarding EWI-2 functions. Expression of EWI-2 in T98G and/or U87-MG malignant glioblastoma cell lines failed to alter two-dimensional cell proliferation but inhibited glioblastoma colony formation in soft agar and caused diminished cell motility and invasion. At the biochemical level, EWI-2 markedly affects the organization of four molecules (tetraspanin proteins CD9 and CD81 and matrix metalloproteinases MMP-2 and MT1-MMP), which play key roles in the biology of astrocytes and gliomas. EWI-2 causes CD9 and CD81 to become more associated with each other, whereas CD81 and other tetraspanins become less associated with MMP-2 and MT1-MMP. We propose that EWI-2 inhibition of glioblastoma growth in vivo is at least partly explained by the capability of EWI-2 to inhibit growth and/or invasion in vitro. Underlying these functional effects, EWI-2 causes a substantial molecular reorganization of multiple molecules (CD81, CD9, MMP-2, and MT1-MMP) known to affect proliferation and/or invasion of astrocytes and/or glioblastomas. |
| Databáze: | OpenAIRE |
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