Milkina E., Ponomarenko A., Korneyko M., Lyakhova I., Zayats Yu., Zaitsev S., Mischenko P., Eliseikina M., Khotimchenko Yu., Shevchenko V., Sharma H., Bryukhovetskiy I.
В журнале Oncology Reports
Год: 2018 Том: 40 Номер: 5 Страницы: 2595-2607
The majority of modern treatment methods for malignant brain tumors are not sufficiently effective, with a median survival time varying between 9 and 14 months. Metastatic and invasive processes are the principal characteristics of malignant tumors. The most important pathogenic mechanism is epithelial-mesenchymal transition (EMT), which causes epithelial cells to become more mobile, and capable of invading the surrounding tissues and migrating to distant organs. Transforming growth factor-ß1 (TGF-ß1) serves a key role in EMT-inducing mechanisms. The current study presented the interaction between hematopoietic stem cells and glioblastoma cells stimulated by TGF-ß1 in vitro. The materials for the study were hematopoietic progenitor cell antigen CD34+ hematopoietic stem cells (HSCs) and U87 glioblastoma cells. Cell culture methods, automated monitoring of cell-cell interactions, confocal laser microscopy, flow cytometry and electron microscopy were used. It was demonstrated that U87 cells have a complex communication system, including adhesive intercellular contacts, areas of interdigitation with dissolution of the cytoplasm, cell fusion, communication microtubes and microvesicles. TGF-ß1 affected glioblastoma cells by modifying the cell shape and intensifying their exocrine function. HSCs migrated to glioblastoma cells, interacted with them and exchanged fluorescent tags. Stimulation of cancer cells with TGF-ß1 weakened the ability of glioblastoma cells to attract HSCs and exchange a fluorescent tag. This process stimulated cancer cell proliferation, which is an indication of the ability of HSCs to ‘switch’ the proliferation and invasion processes in glioblastoma cells.
