The Paired Siglecs in Brain Tumours Therapy: The Immunomodulatory Effect of Dexamethasone and Temozolomide in Human Glioma In Vitro Model
| Autor: | Robert Czarnomysy, Natalia Wawrusiewicz-Kurylonek, Halina Car, Krzysztof Bielawski, Przemyslaw Wielgat, Karol Rogowski |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
THP-1 Cells
Antigens Differentiation Myelomonocytic microglia dexamethasone temozolomide Biology Catalysis Article Flow cytometry Inorganic Chemistry lcsh:Chemistry Immune system Antigens CD Lectins Glioma glioma Antineoplastic Combined Chemotherapy Protocols medicine Humans Immunologic Factors Physical and Theoretical Chemistry Molecular Biology lcsh:QH301-705.5 Spectroscopy Temozolomide Microglia medicine.diagnostic_test Brain Neoplasms Organic Chemistry Membrane Proteins SIGLEC General Medicine respiratory system medicine.disease Fusion protein Computer Science Applications medicine.anatomical_structure lcsh:Biology (General) lcsh:QD1-999 Siglec biology.protein Cancer research Antibody medicine.drug |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 4 International Journal of Molecular Sciences, Vol 22, Iss 1791, p 1791 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22041791 |
| Popis: | The paired sialic acid-binding immunoglobulin like lectins (Siglecs) are characterized by similar cellular distribution and ligand recognition but opposing signalling functions attributed to different intracellular sequences. Since sialic acid—Siglec axis are known to control immune homeostasis, the imbalance between activatory and inhibitory mechanisms of glycan-dependent immune control is considered to promote pathology. The role of sialylation in cancer is described, however, its importance in immune regulation in gliomas is not fully understood. The experimental and clinical observation suggest that dexamethasone (Dex) and temozolomide (TMZ), used in the glioma management, alter the immunity within the tumour microenvironment. Using glioma-microglia/monocytes transwell co-cultures, we investigated modulatory action of Dex/TMZ on paired Siglecs. Based on real-time PCR and flow cytometry, we found changes in SIGLEC genes and their products. These effects were accompanied by altered cytokine profile and immune cells phenotype switching measured by arginases expression. Additionally, the exposure to Dex or TMZ increased the binding of inhibitory Siglec-5 and Siglec-11 fusion proteins to glioma cells. Our study suggests that the therapy-induced modulation of the interplay between sialoglycans and paired Siglecs, dependently on patient’s phenotype, is of particular signification in the immune surveillance in the glioma management and may be useful in glioma patient’s therapy plan verification. |
| Databáze: | OpenAIRE |
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