Glioblastoma multiforme (GBM) tumors, which arise from glia in the central nervous system (CNS), are one of the most deadly forms of human cancer with a median survival time of similar to 1 year. Their high infiltrative capacity makes them extremely difficult to treat, and even with aggressive multimodal clinical therapies, outcomes are dismal. To improve understanding of cell migration in these tumors, three-dimensional (3D) multicomponent composite hydrogels consisting of collagen and hyaluronic acid, or hyaluronan (HA), were developed. Collagen is a component of blood vessels known to be associated with GBM migration; whereas, HA is one of the major components of the native brain extracellular matrix (ECM). We characterized hydrogel microstructural features and utilized these materials to investigate patient tumor-derived, single cell morphology, spreading, and migration in 3D culture. GBM morphology was influenced by collagen type with cells adopting a rounded morphology in collagen-IV versus a spindle-shaped morphology in collagen-I/III. GBM spreading and migration were inversely dependent on HA concentration; with higher concentrations promoting little or no migration. Further, noncancerous astrocytes primarily displayed rounded morphologies at lower concentrations of HA; in contrast to the spindle-shaped (spread) morphologies of GBMs. These results suggest that GBM behaviors are sensitive to ECM mimetic materials in 3D and that these composite hydrogels could be used to develop 3D brain mimetic models for studying migration processes.
Glioblastoma Behaviors in Three-Dimensional Collagen-Hyaluronan Composite Hydrogels
Creators
Shreyas S. Rao - The Ohio State University
Jessica DeJesus - The Ohio State University
Aaron R. Short - The Ohio State University
Jose J. Otero - The Ohio State University
Atom Sarkar - Geisinger Health System
Jessica O. Winter - The Ohio State University
Publication Details
ACS applied materials & interfaces, v 5(19), pp 9276-9284
Publisher
Amer Chemical Soc
Number of pages
9
Grant note
Pelotonia Graduate Fellowship
CBET BME 0854015 / National Science Foundation; National Science Foundation (NSF)
Women in Philanthropy, OSU
P30CA016058 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
H.C. "Slip" Slider Professorship
Resource Type
Journal article
Language
English
Academic Unit
Neurology; Neurosurgery
Web of Science ID
WOS:000326356600005
Scopus ID
2-s2.0-84885437982
Other Identifier
991021960813204721
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Collaboration types
Domestic collaboration
Web of Science research areas
Materials Science, Multidisciplinary
Nanoscience & Nanotechnology
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