中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (11): 1816-1822.doi: 10.4103/1673-5374.219030

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

血管内皮生长因子和辐射对多形性胶质母细胞瘤细胞间隙连接细胞间通讯的影响

  

  • 收稿日期:2017-09-25 出版日期:2017-11-15 发布日期:2017-11-15

Influence of vascular endothelial growth factor and radiation on gap junctional intercellular communication in glioblastoma multiforme cell lines

Reinhardt Krcek1, Pauline Latzer1, Irenäus Anton Adamietz2, Helmut Bühler3, Carsten Theiss1   

  1. 1 Institute of Anatomy, Department of Cytology, Ruhr-University Bochum, Bochum, North Rhine-Westphalia, Germany
    2 Department of Radiotherapy and Radio-Oncology, University Medical Centre Marienhospital, Ruhr-University Bochum, Herne, North Rhine-Westphalia, Germany
    3 Institute for Molecular Oncology, Radio-Biology and Experimental Radiotherapy, University Medical Centre Marienhospital, Ruhr-University Bochum, Herne, North Rhine-Westphalia, Germany
  • Received:2017-09-25 Online:2017-11-15 Published:2017-11-15
  • Contact: Carsten Theiss, Ph.D.,carsten.theiss@rub.de.

Abstract:

 

Glioblastoma multiforme (GBM) is a highly aggressive glial brain tumor with an unfavorable prognosis despiteall current therapies including surgery, radiation and chemotherapy. One characteristic of this tumor is a strong synthesis of vascular endothelial growth factor (VEGF), an angiogenesis factor, followed by pronounced vascularization. VEGF became a target in the treatment of GBM, for example with bevacizumab or the tyrosine kinase inhibitor axitinib, which blocks VEGF receptors. To improve patients’ prognosis, new targets in the treatment of GBM are under investigations. The role of gap junctions in GBM remains unknown, but some experimental therapies affect these intercellular channels to treat the tumor. Gap junctions are composed of connexins to allow the transport of small molecules between adjacent cells through gap junctional intercellular communication (GJIC). Based on data derived from astrocytes in former studies, which show that VEGF is able to enhance GJIC, the current study analyzed the effects of VEGF, radiation therapy and VEGF receptor blockade by axitinib on GJIC in human GBM cell lines U-87 and U-251. While VEGF is able to induce GJIC in U-251 cells but not in U-87 cells, radiation enhances GJIC in both cell lines. VEGF receptor blockade by axitinib diminishes radiation induced effects in U-251 partially, while increases GJIC in U-87 cells. Our data indicate that VEGF and radiation are both modifying components of GJIC in pathologic brain tumor tissue.

Key words: cell communication, vascular endothelial growth factor, irradiation, vascular endothelial growth factor-receptor blockade, glioma, neurobiotin, connexin, cell culture, immunohistochemistry, microinjection