title: Impact of the biophysical features of a 3D gelatin microenvironment on glioblastoma malignancy.
abstract: Three-dimensional tissue engineered constructs provide a platform to examine how the local extracellular matrix (ECM) contributes to the malignancy of cancers such as human glioblastoma multiforme. Improved resolution of how local matrix biophysical features impact glioma proliferation, genomic and signal transduction paths, as well as phenotypic malignancy markers would complement recent improvements in our understanding of molecular mechanisms associated with enhanced malignancy. Here, we report the use of a gelatin methacrylate (GelMA) platform to create libraries of three-dimensional biomaterials to identify combinations of biophysical features that promote malignant phenotypes of human U87MG glioma cells. We noted key biophysical properties, namely matrix density, crosslinking density, and biodegradability, that significantly impact glioma cell morphology, proliferation, and motility. Gene expression profiles and secreted markers of increased malignancy, notably VEGF, MMP-2, MMP-9, HIF-1, and the ECM protein fibronectin, were also significantly impacted by the local biophysical environment as well as matrix-induced deficits in diffusion-mediated oxygen and nutrient biotransport. Overall, this biomaterial system provides a flexible platform to explore the role biophysical factors play in the etiology, growth, and subsequent invasive spreading of gliomas.
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
authors.forename: S
authors.initials: S
authors.lastname: Pedron
authors.forename: B A C
authors.initials: BA
authors.lastname: Harley
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D055592:Biophysical Phenomena; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D004058:Diffusion; D005780:Gelatin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008689:Methacrylates / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D009389:Neovascularization, Pathologic / Q000235:genetics; D010641:Phenotype; D011092:Polyethylene Glycols / Q000494:pharmacology; D034421:Sus scrofa; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008689:Methacrylates; D042461:Vascular Endothelial Growth Factor A; C437167:poly(ethylene glycol)diacrylate; D011092:Polyethylene Glycols; D005780:Gelatin
keywords: biophysical properties; gelatin; glioblastoma; malignancy; tumor microenvironment