# The oncogenic functions of Neuropilin-1 in the glioblastoma tumor microenvironment

> **NIH NIH F30** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $36,401

## Abstract

Abstract
Glioblastoma (GB) is the most common primary tumor of the central nervous system (CNS) in adults. Despite
aggressive surgery, radiation, and chemotherapy, median survival is only 15-20 months. In GB tumors,
approximately 30-50% of the cells in the tumor are innate myeloid immune cells, primarily macrophages (MP)
and microglia (MG). Research in the Tsirka laboratory has shown that MP and MG enhance GB growth by
promoting angiogenesis and fostering an immunosuppressive tumor microenvironment (TME), partly through
the action of the co-receptor Neuropilin-1 (NRP1). Our recent work has suggested distinct roles for MG and MP
in glioma. Expression of NRP1 on glioma-associated MP and MG (GAM) is critical for their oncogenic activity.
Deletion of NRP1 from myeloid cells blunts angiogenesis and results in decreased GB volume. Prior research
has shown that hypoxic glioma cells upregulate stem cell-associated genes and function as glioma stem cells
(GSC), which are thought to drive the immunosuppressive and angiogenic nature of GAM. NRP1 has been
shown to be critical for the GAM responses to hypoxia. The long-term goal of our research group is to define the
TME roles of MG and MP as well as methods through which MP and MG can be repolarized to exert anti-
tumorigenic effects rather than facilitate tumor growth. The overall objective of my proposal is to determine the
mechanisms by which MG and MP interact with hypoxic regions and GSC to exert oncogenic effects. I
hypothesize that NRP1 activation on myeloid cells is an important mediator for pro-tumorigenic signaling
between hypoxic glioma cells, GSC and GAM. To test this hypothesis, I will pursue two specific aims: 1)
Determine the NRP1 pathways activated in GAM by hypoxic glioma cells; and 2) identify how GAM-NRP1
signaling affects the interaction between GSC and GAM. For the first aim, MP and MG will be separately treated
with media from glioma cells cultured in normoxia or hypoxia, with or without a NRP1 inhibitor, and assessed for
differences in the expression of pro/anti-inflammatory and angiogenesis factors identified through
phosphoproteomics. Using immunocompetent mouse models of GB, I will investigate how GAM-NRP1 affects
GAM phenotypes and tumor cell proliferation in normoxic and hypoxic tumor regions. In the second aim, the
contribution of GAM-NRP1 to GSC/GAM interactions will be interrogated in culture and in vivo. The proposed
research is expected to be significant because it will determine roles for MP and MG behavior in the context of
hypoxic areas of glioma and further explore the interaction between GSC and GAM. It will also help determine
whether modulation of NRP1 is a viable method for promoting anti-tumorigenic outputs for GAM.

## Key facts

- **NIH application ID:** 10312975
- **Project number:** 1F30CA257677-01A1
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Daniel Radin
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,401
- **Award type:** 1
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312975

## Citation

> US National Institutes of Health, RePORTER application 10312975, The oncogenic functions of Neuropilin-1 in the glioblastoma tumor microenvironment (1F30CA257677-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10312975. Licensed CC0.

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