Abstract
Dynamic alterations in the unique brain extracellular matrix (ECM) are involved in malignant brain tumors. Yet studies of brain ECM roles in tumor cell behavior have been difficult due to lack of access to the human brain. We present a tunable 3D bioengineered brain tissue platform by integrating microenvironmental cues of native brain-derived ECMs and live imaging to systematically evaluate patient-derived brain tumor responses. Using pediatric ependymoma and adult glioblastoma as examples, the 3D brain ECM-containing microenvironment with a balance of cell-cell and cell-matrix interactions supports distinctive phenotypes associated with tumor type-specific and ECM-dependent patterns in the tumor cells’ transcriptomic and release profiles. Label-free metabolic imaging of the composite model structure identifies metabolically distinct sub-populations within a tumor type and captures extracellular lipid-containing droplets with potential implications in drug response. The versatile bioengineered 3D tumor tissue system sets the stage for mechanistic studies deciphering microenvironmental role in brain tumor progression.
Highlights
Many brain tumors have dismal prognosis, especially glioblastoma (GBM) and those that typically occur in young children, such as ependymoma
A decellularization approach was undertaken since little is known about brain extracellular matrix (ECM) during development and ECM proteins are mostly conserved over species, such that porcine brains can be used to extract a mixture of native brain-ECM27
The competition between tumor cell cohesion and interactions with the surrounding ECM is purported to dictate the invasive behavior of brain tumors and their drug sensitivity[45]
Summary
Many brain tumors have dismal prognosis, especially glioblastoma (GBM) and those that typically occur in young children, such as ependymoma. We have attempted to develop an in vitro platform system to examine the dynamic interactions of a brain-ECM-containing microenvironment with different primary brain tumors. While several CSPGs are upregulated in GBM progression[7], CSPGs may prevent diffuse invasion of tumor cells[15]. These studies have provided evidence of brain-ECM involvement in tumor progression; yet it is unclear how different tumors alter their ECM environment by the tumor cells’ reciprocal signaling. In order to understand the dynamic cell-ECM interactions, it is critical to separately define the contributions of ECM components towards brain tumor development, progression, and tumor-type-specific responses. In our in vitro platform system, we incorporate developmentally sourced brain-ECM cues, with the aim of capturing some of these dynamic tumor cell-ECM responses
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
