Article
Differences in the expression of CD184, CD95, CD178 and CD40 in human gliomas of various grades, before and after chemotherapy
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Authors
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Jan Werner
- Labor für Neuroonkologie und experimentelle Neurochirurgie, Klinik für Allgemeine Neurochirurgie, Zentrum für Neurochirurgie, Universitätsklinikum Köln, Köln
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Gabriele Röhn
- Labor für Neuroonkologie und experimentelle Neurochirurgie, Klinik für Allgemeine Neurochirurgie, Zentrum für Neurochirurgie, Universitätsklinikum Köln, Köln
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Roland Goldbrunner
- Labor für Neuroonkologie und experimentelle Neurochirurgie, Klinik für Allgemeine Neurochirurgie, Zentrum für Neurochirurgie, Universitätsklinikum Köln, Köln
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Marco Timmer
- Labor für Neuroonkologie und experimentelle Neurochirurgie, Klinik für Allgemeine Neurochirurgie, Zentrum für Neurochirurgie, Universitätsklinikum Köln, Köln
| Published: | June 2, 2015 |
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Outline
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Objective: Cell surface molecules (CDs) are very important in diagnostics and a cornerstone in the process of understanding the behavior of tumors. A better understanding of the immunological surface of human glioma cells could lead to a deeper understanding of tumor-invasion, -progress and potential therapies.
Method: Samples of different tumors were tested and compared. Groups were divided into WHO °II-, °III-tumors, °III-tumor relapse, primary glioblastoma (GBM) ± chemotherapy, secondary GBM ± chemotherapy and a control group with peritumoral tissue. Immunohistochemical staining with DAB and counterstaining with hematoxylin was performed with antibodies against CD184, CD95 and CD40 with 4 samples per group. Quantitative real-time PCR was performed and the relative expression levels of CD184, CD95, CD178 and CD40 analyzed; SDHA was used as a housekeeping gene. The cDNA was synthesized from RNA from 80 frozen human tumor samples, divided in the groups as described above, each group consisting of 10 samples. Moreover, human primary GBM cells were injected into the striatum of immunodeficient rats. These were treated with temozolomide or a control agent, respectively, in order to confirm the effects seen on the different CDs before and after chemotherapy in the human tumor samples in vivo.
Results: Both CD184 and CD95 showed a stronger staining in immunohistochemistry than CD40. In intra-group comparison, CD184, CD95 and CD40 showed increasing staining within rising WHO grade, whilst CD184 and CD95 made a big increase comparing °II and °III tumors, CD40 showed increasing staining comparing °III tumors and GBM. In quantitative real-time PCR, a significant higher expression level of CD95 and CD184 was found in primary glioblastoma, compared to the control tissue (p<0.05), also CD95 showed a higher expression in primary compared to secondary GBM (p<0.05).
Conclusions: Stronger expression of cell surface molecules in higher-grade gliomas implicates an immunological change in the cell surface in the progression of low-grade tumors towards GBM. The difference of expression in primary and secondary GBM underlines the different genesis of these tumors. For a deeper understanding of mechanisms in tumor immunology of gliomas, further studies are necessary.
