# Establishment of immunocompetent spontaneous glioma model to study glioma-associated astrocytes

> **NIH NIH R21** · VIRGINIA COMMONWEALTH UNIVERSITY · 2021 · $426,938

## Abstract

Astrocytes play critical physiological functions in the brain. However, in response to diverse
insults, astrocytes become reactive and help to restore homeostasis. Their responses can also
turn pathological as observed in chronic inflammation and brain tumors. Reactive astrocytes (RA)
and their responses have recently been recognized as key players in the microenvironment of
both primary and metastatic brain tumors. Recently a subset of RA with activated STAT3 has
been shown to be critical for supporting growth of both brain metastatic lesions as well as
glioblastoma cells (GBM). Although activation of STAT3 in RA supports the growth of GBM cells,
mechanisms that drive STAT3 activation in RA remain elusive. While a plethora of cytokines and
growth factors induce temporal STAT3 activation, a bioactive sphingolipid, sphingosine-1-
phosphate (S1P) can drive persistent activation of STAT3 via its G-protein-coupled receptor 1
(S1PR1). S1PR1 is highly expressed by astrocytes, and deletion of S1PR1 in astrocytes limits
their reactivity, while sphingosine kinase 1 generating S1P is overexpressed in GBM. These
findings raise a possibility that GBM-derived S1P activates STAT3 in RA via the
S1P/S1PR1/STAT3 axis. Nevertheless, the major obstacle in studying the mechanisms of RA
activation is the lack of appropriate glioma model that would allow genetic manipulation
specifically in these cells. We have recently further developed a previously established
spontaneous mouse glioma model, which will allow us to test the importance of genes in RA. We
will examine the usefulness of our model to study RA, and test whether the S1P/S1PR1/STAT3
axis drives gene expression programs that re-wire RA leading to establishment of an
immunosuppressive state. We will also determine whether S1PR1 inhibition affects
preestablished gliomas.

## Key facts

- **NIH application ID:** 10212500
- **Project number:** 1R21NS118359-01A1
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** TOMASZ K KORDULA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $426,938
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212500

## Citation

> US National Institutes of Health, RePORTER application 10212500, Establishment of immunocompetent spontaneous glioma model to study glioma-associated astrocytes (1R21NS118359-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10212500. Licensed CC0.

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