title: Investigating the Influence of HUVECs in the Formation of Glioblastoma Spheroids in High-Throughput Three-Dimensional Microwells.
abstract: Glioblastoma (GBM) is the most common form of primary brain tumor with a high infiltrative capacity, increased vascularity, and largely elusive tumor progression mechanism. The current GBM treatment methods do not increase the patient survival rate and studies using two-dimensional (2D) cell cultures and in vivo animal models to investigate GBM behavior and mechanism have limitations. Therefore, there is an increasing need for in vitro three-dimensional (3D) models that closely mimic in vivo microenvironment of the GBM tumors to understand the underlying mechanisms of the tumor progression. In this study we propose to use a 3D in vitro model to overcome these limitations, using poly (ethylene glycol) dimethyl acrylate (PEGDA) hydrogel-based microwells and co-culture GBM (U87) cells and endothelial cells (HUVEC) in the 3D microwells to provide a 3D in vitro simulation of the tumor microenvironment. Furthermore, we investigated the gene expression differences of co-cultures by quantitative real-time PCR. Our results suggested that the relative expression profiles of tumor angiogenesis markers, PECAM1/CD31, and VEGFR2, in co-cultures are consistent with in vivo GBM studies. Furthermore, we suggest that our microwell platform could provide robust and useful 3D co-culture models for high-throughput drug screening and treatment of the GBM.
authors.forename: Naze G
authors.initials: NG
authors.lastname: Avci
authors.forename: Yantao
authors.initials: Y
authors.lastname: Fan
authors.forename: Andrei
authors.initials: A
authors.lastname: Dragomir
authors.forename: Yasemin M
authors.initials: YM
authors.lastname: Akay
authors.forename: Metin
authors.initials: M
authors.lastname: Akay
mesh_terms: D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000295:instrumentation*; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005909:Glioblastoma / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D056656:Lab-On-A-Chip Devices; D018874:Spheroids, Cellular / Q000473:pathology / Q000502:physiology; D059016:Tumor Microenvironment / Q000502:physiology*