Format

Send to

Choose Destination
Gels. 2017 Jul 13;3(3). pii: E28. doi: 10.3390/gels3030028.

Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform.

Author information

1
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. hsivakum@wakehealth.edu.
2
Department of Neurology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. rstrowd@wakehealth.edu.
3
Comprehensive Cancer Center at Wake Forest Baptist, Wake Forest Baptist Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA. rstrowd@wakehealth.edu.
4
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. askardal@wakehealth.edu.
5
Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. askardal@wakehealth.edu.
6
Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. askardal@wakehealth.edu.
7
Comprehensive Cancer Center at Wake Forest Baptist, Wake Forest Baptist Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA. askardal@wakehealth.edu.

Abstract

Glioblastoma (GBM) is one of most aggressive forms of brain cancer, with a median survival time of 14.6 months following diagnosis. This low survival rate could in part be attributed to the lack of model systems of this type of cancer that faithfully recapitulate the tumor architecture and microenvironment seen in vivo in humans. Therapeutic studies would provide results that could be translated to the clinic efficiently. Here, we assess the role of the tumor microenvironment physical parameters on the tumor, and its potential use as a biomarker using a hyaluronic acid hydrogel system capable of elastic modulus tuning and dynamic elastic moduli changes. Experiments were conducted to assess the sensitivity of glioblastoma cell populations with different mutations to varying elastic moduli. Cells with aberrant epithelial growth factor receptor (EGFR) expression have a predilection for a stiffer environment, sensing these parameters through focal adhesion kinase (FAK). Importantly, the inhibition of FAK or EGFR generally resulted in reversed elastic modulus preference. Lastly, we explore the concept of therapeutically targeting the elastic modulus and dynamically reducing it via chemical or enzymatic degradation, both showing the capability to reduce or stunt proliferation rates of these GBM populations.

KEYWORDS:

elastic modulus; epidermal growth factor receptor; glioblastoma; hydrogel; tumor growth

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center