# Cellular Crosstalk Between Glioma and Blood-brain Barrier Endothelia

> **NIH NIH P20** · UNIVERSITY OF IDAHO · 2020 · $152,010

## Abstract

This Administrative Supplement to University of Idaho INBRE Program establishes an INBRE-COBRE
research collaboration. The project, Cellular Crosstalk Between Glioma and Blood-brain Barrier Endothelia,
brings together a neurobiologist and a cell physiologist to study glioblastoma multiforme, an aggressive brain
cancer. The INBRE-Developmental Research Program Investigator, R. L. Daniels, and COBRE-project
investigator, R.S. Beard will combine their talents and expertise. The partnership will enhance the quality of
scientific work for both investigators and increase research opportunities for undergraduate students. Their
long-term goal is to better understand the cellular and molecular basis of glioblastoma multiforme pathobiology.
Basic knowledge will contribute to future effective therapies. The hypothesis to be tested is that tumor-induced
hypoxia initiates a positive-feedback loop between glioma cells and blood-brain barrier endothelia that
ultimately promotes tumor growth and migration. Strong preliminary data supports this idea. The Daniels
laboratory will use their expertise in culturing glioma cells and measuring cell signaling to test if hypoxic blood-
brain epithelia release enough ATP to induce glutamate discharge from recipient tumor cells. Conditioned
media from blood-brain barrier endothelia grown for various times in normal or hypoxic conditions will be used
(provided by the Beard laboratory). ATP in conditioned media will be measured with a colorimetric assay and
the media tested in glioma cultures. Calcium signaling coupled to glutamate secretion will be measured with a
ratiometric calcium probe and high-performance liquid chromatography. Finally, the role of the P2X7 receptor
in the mechanism of this cellular crosstalk will be confirmed using a receptor agonist, siRNA silencing, and
measuring receptor gene expression. The Beard laboratory will use their expertise in culturing blood-brain
barrier endothelia and measuring cell signaling to test if glioma-derived glutamate directly induces barrier
dysfunction. The contribution of glioma-derived glutamate to blood-brain barrier dysfunction by triggering the
glutamate receptor, NMDAr, activation will be evaluated. The same cell culture models used in the Daniels
laboratory will be used except that mechanistic endpoints will evaluate endothelia barrier disruption in the
hypoxic microenvironment surrounding necrotic cores in glioblastoma multiforme tumors. Comparable
endothelia-injury studies will include challenging barrier endothelia monolayers with 1) glutamate, 2)
conditioned medium from ATP-stimulated glioma, 3) conditioned medium from glioma cells or astrocytes grown
under hypoxic conditions, and 4) the direct effect on barrier dysfunction induced by co-culturing endothelia with
glioma cells in hypoxic conditions using luminal/abluminal chambers of COL4-coated transwell inserts. The
Daniels-Beard collaboration has strong institutional support and will use lDeA-built research core...

## Key facts

- **NIH application ID:** 10152261
- **Project number:** 3P20GM103408-20S2
- **Recipient organization:** UNIVERSITY OF IDAHO
- **Principal Investigator:** Richard Scott Beard
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $152,010
- **Award type:** 3
- **Project period:** 2001-09-30 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152261

## Citation

> US National Institutes of Health, RePORTER application 10152261, Cellular Crosstalk Between Glioma and Blood-brain Barrier Endothelia (3P20GM103408-20S2). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10152261. Licensed CC0.

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