Interaction of hematopoietic CD34+ CD45+ stem cells and cancer cells stimulated by TGF‑β1 in a model of glioblastoma in vitro

Milkina,Elena; Ponomarenko,Arina; Korneyko,Maria; Lyakhova,Irina; Zayats,Yulia; Zaitsev,Sergey; Mischenko,Polina; Eliseikina,Marina; Khotimchenko,Yuri; Shevchenko,Valeryi; Sharma,Hari; Bryukhovetskiy,Igor

doi:10.3892/or.2018.6671

Interaction of hematopoietic CD34+ CD45+ stem cells and cancer cells stimulated by TGF‑β1 in a model of glioblastoma in vitro

Authors:
- Elena Milkina
- Arina Ponomarenko
- Maria Korneyko
- Irina Lyakhova
- Yulia Zayats
- Sergey Zaitsev
- Polina Mischenko
- Marina Eliseikina
- Yuri Khotimchenko
- Valeryi Shevchenko
- Hari Sharma
- Igor Bryukhovetskiy
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Affiliations: School of Biomedicine of The Far Eastern Federal University, Vladivostok 690091, Russia, School of Biomedicine of The Far Eastern Federal University, Vladivostok 690091, Russia, National Scientific Center of Marine Biology FEB RAS, Vladivostok 690041, Russia, International Experimental CNS Injury & Repair (IECNSIR), Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, University Hospital, Uppsala University, Uppsala, SE‑75185, Sweden
Published online on: August 24, 2018 https://doi.org/10.3892/or.2018.6671
Pages: 2595-2607
Copyright: © Milkina et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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‑β1 (TGF‑β1) serves a key role in EMT‑inducing mechanisms. The current study presented the interaction between hematopoietic stem cells and glioblastoma cells stimulated by TGF‑β1 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‑β1 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‑β1 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.

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