Modeling microenvironmental regulation of glioblastoma stem cells: a biomaterials perspective
- 1Barrow Brain Tumor Research Center, Barrow Neurological Institute (BNI), United States
- 2School of Biological and Health Systems Engineering, Arizona State University, United States
Following diagnosis of a glioblastoma (GBM) brain tumor, surgical resection, chemotherapy and radiation together yield a median patient survival of only 15 months. Importantly, standard treatments fail to address the dynamic regulation of the brain tumor microenvironment that actively supports tumor progression and treatment resistance. It is becoming increasingly recognized that specialized niches within the tumor microenvironment maintain a population of highly malignant glioblastoma stem-like cells (GSCs). GSCs are resistant to traditional chemotherapy and radiation therapy, suggesting that they may be responsible for the near universal rates of tumor recurrence and associated morbidity in GBM. Thus, disrupting microenvironmental support for GSCs could be critical to developing more effective GBM therapies. Three-dimensional (3D) culture models of the tumor microenvironment are powerful tools for identifying key biochemical and biophysical inputs that impact malignant behaviors. Such systems have been used effectively to identify conditions that regulate GSC proliferation, invasion, stem-specific phenotypes, and treatment resistance. Considering the significant role that GSC microenvironments play in regulating this tumorigenic sub-population, these models may be essential for uncovering mechanisms that limit GSCs malignancy.
Keywords: Tumor Microenvironment, Niche microenvironments, Brain tumor stem cells (BTSCs), cancer stem cells (CSCs), scaffolds, Hydrogels, three-dimensional cell culture
Received: 27 Oct 2017;
Accepted: 26 Jan 2018.
Edited by:Sara Pedron, University of Illinois at Urbana–Champaign, United States
Reviewed by:Nor Eddine Sounni, University of Liège, Belgium
Joseph Chen, University of California, Berkeley, United States
Ece Ozturk, Columbia University, United States
Copyright: © 2018 Heffernan and Sirianni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Rachael W. Sirianni, Barrow Neurological Institute (BNI), Barrow Brain Tumor Research Center, 350 W Thomas Road, Neural Research Center 441, Phoenix, 85013, AZ, United States, firstname.lastname@example.org