# Role of Receptor for Advanced Glycation End Product (RAGE) Pathway in Brain Tumors

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $407,551

## Abstract

PROJECT SUMMARY
Malignant gliomas are aggressive tumors that often recur within the resection margin after treatment. In
addition to the development of targeted therapies against neoplastic cells, treatments aimed at tumor stroma
are being considered to enhance conventional therapies. Tumor-associated inflammatory cells, such as
macrophages and neutrophils, comprise a significant component of the glioma stroma and actively participate
in angiogenesis, invasion and metastasis. These myeloid-derived cells express pattern recognition receptors
such as the receptor for advanced glycation endproducts (RAGE) that constantly monitor the tumor micro-
environment (TME). Engagement of RAGE by its ligands results in activation of multiple downstream pathways
that regulate cell proliferation, survival, differentiation, migration, phagocytosis and autophagy. During the
previous funding cycle, we demonstrated that upregulation of a common glioma RAGE ligand, S100B,
promoted macrophage recruitment and altered their conversion into tumor-promoting cells. Furthermore, we
showed that genetic ablation of RAGE in TME prolonged survival of glioma-bearing mice by attenuating tumor-
associated inflammation and angiogenesis. These studies also revealed significant variability in the expression
of other RAGE ligands in animal glioma models. The objective of this competing renewal is to evaluate the
role of the RAGE pathway on TME remodeling and tumor progression in gliomas. Our central hypothesis is
that gliomas release RAGE ligands that contribute to the polarization of inflammatory cells, and promote tumor
growth and invasion. To test this, we propose the following experiments. In Aim 1 we will measure RAGE
ligands in human glioma tumor samples in order to determine their physiological concentrations in the TME.
Aim 2 will characterize changes in tumor inflammation after inhibition of RAGE ligands. Finally in Aim 3, we
will determine the effect of RAGE activation on glioma progression and optimize the antitumor activity of
targeting the RAGE axis. These studies will provide the first insights into the effect of the RAGE pathway and
surgical trauma on glioma recurrence. This critically needed understanding of the mechanism of immune
evasion in gliomas will be valuable in optimizing antiglioma therapies.

## Key facts

- **NIH application ID:** 9899943
- **Project number:** 5R01CA155769-09
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Behnam Badie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $407,551
- **Award type:** 5
- **Project period:** 2011-09-07 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899943

## Citation

> US National Institutes of Health, RePORTER application 9899943, Role of Receptor for Advanced Glycation End Product (RAGE) Pathway in Brain Tumors (5R01CA155769-09). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9899943. Licensed CC0.

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