Abstract

Cellular communication plays a crucial role in the coordination and organization of cancer cells. Especially processes such as uncontrolled cell growth, invasion, and therapy resistance (development), which are features of very malignant tumors like glioblastomas, are supported by an efficient cell-to-cell communication in the tumor environment. One powerful way for cells to communicate are tunneling nanotubes (TNTs). These tiny membrane tunnels interconnect cells over long distances and serve as highways for information exchange between distant cells. Here, we study the response of cellular communication via TNTs in U87 glioblastoma cells to homogeneous irradiation with α-particles as a stress factor. We describe the development of TNT networks in certain time steps after irradiation using confocal live-cell imaging and suggest an evaluation method to characterize these communication networks. Our results show that irradiated cells establish their network faster and have more cell-to-cell connections with high TNT content than sham-irradiated controls within the first 24 h. These findings suggest that there is an additional trigger upon radiation damage which results in fast and intensive network formation by TNTs as a radiation damage response mechanism.

Highlights

  • Glioblastomas are one of the most common and most aggressive brain tumors, which are characterized by their high invasiveness and recurrence

  • We introduced a method to examine tunneling nanotube (TNT) networks in vitro in a quantitative and qualitative manner with the aim to obtain a better understanding of cellular communication networks

  • We figured out that the cellular communication via TNTs is influenced by radiation in U87 glioblastoma cells

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Summary

Introduction

Glioblastomas are one of the most common and most aggressive brain tumors, which are characterized by their high invasiveness and recurrence. Patients have a median survival of no more than 15 months and show a five-year survival rate below 10% [1,2,3] This poor prognosis is a result of the aggressive nature of glioblastomas composed of genomic instability, uncontrolled cellular proliferation, intratumoral heterogeneity, resistance to apoptosis, and high diffuse infiltration rates into the surrounding tissue [4,5,6,7]. Due to these features, glioblastomas exhibit a considerably high chemo- and radioresistance, and despite extensive research on glioblastoma treatment, the responsible mechanisms for the aggressive nature are poorly understood or even unknown. Radiotherapy is, besides surgery and chemotherapy, mostly in combination with one or even both, the treatment of choice for glioblastoma for ∼50% of all treated tumors worldwide [8, 9].

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