# Interstitial Fluid Flow Regulates Glioma Cell Invasion

> **NIH NIH R37** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2021 · $476,966

## 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:** 10057362
- **Project number:** 5R37CA222563-04
- **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:** 2021
- **Award amount:** $476,966
- **Award type:** 5
- **Project period:** 2017-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057362

## Citation

> US National Institutes of Health, RePORTER application 10057362, Interstitial Fluid Flow Regulates Glioma Cell Invasion (5R37CA222563-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10057362. Licensed CC0.

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