# Interstitial Fluid Flow Regulates Glioma Cell Invasion

> **NIH NIH R37** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2024 · $508,646

## Abstract

Project Summary
Glioblastoma, the deadliest form of brain cancer, is defined by the invasive nature of its cells.
Invasion in the brain follows distinctive routes that correlate with interstitial and bulk flow
pathways. In brain cancer, increased interstitial fluid flow develops due to the increase in
interstitial pressure in the tumor bulk interfacing with the relatively normal pressure of the
surrounding brain tissue, or tumor microenvironment. This differential leads to fluid transport
specifically across the invasive edge of the tumor where cells are prone to both interact with the
surrounding brain tissue and to evade localized, transport-limited therapies. To examine how
interstitial fluid flow affects the invasion of brain cancer cells, we have developed in vitro and in
vivo methods to examine fluid flow responses. In vitro, we have found that interstitial flow
enhances invasion of brain cancer cells using both cell lines and patient-derived glioma stem cells
in tissue-engineered models of the brain-tumor interface via the chemokine/receptor pair
CXCL12/CXCR4. In vivo, we have seen interstitial flow and increase invasion of implanted cancer
cells through the brain in part through this same mechanism. By conducting in vivo measurements
of interstitial flow using MRI we have correlated regions of interstitial fluid flow, glioma invasion,
and glial gene expression of the receptor sphingosine-1-phosphate 3. In this proposal, we will
examine the role of interstitial fluid flow as a driving factor of glioma invasion. To make a case for
the importance of interstitial flow in regulating GBM invasion first, we will elucidate the true nature
of interstitial flow in the in vivo GBM microenvironment. We will accomplish this utilizing clinically
relevant imaging and computational tools to probe the prevalence of flow as the tumor develops,
and determine regions in which flow is the highest. Second, we will determine the contributions
of interstitial flow at the level of cancer cell invasion. We will observe invasion patterns of multiple
patient-derived glioblastoma stem cells in the specifically interrogating the mechanism of
CXCR4/CXCL12-mediated autologous chemotaxis, a novel mechanism of invasion only possible
under flow. Finally, we will use our unique ability to tissue engineer the glioblastoma
microenvironment to examine the role of glial-expressed S1PR3 under flow on glioma invasion.
Altogether, these reports will advance the importance and strategies for mitigating interstitial flow
and its effects in GBM and offer modalities by which to study further effects of flow on therapeutic
response. Understanding the impact of interstitial flow will ultimately help predict areas of GBM
progression and recurrence.
.

## Key facts

- **NIH application ID:** 10772966
- **Project number:** 5R37CA222563-07
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Jennifer M Munson
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $508,646
- **Award type:** 5
- **Project period:** 2022-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10772966

## Citation

> US National Institutes of Health, RePORTER application 10772966, Interstitial Fluid Flow Regulates Glioma Cell Invasion (5R37CA222563-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10772966. Licensed CC0.

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