# Analyzing Cell-Cell Fusion in Glioblastoma Growth and Progression

> **NIH NIH R21** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $200,000

## Abstract

ABSTRACT
Cell-cell fusion promotes the development and physiology of most organs and has been
documented in diseases including multiple types of cancer. Various reports have shown that
stromal cells in the tumor microenvironment can fuse with neoplastic cells to generate malignant
hybrid progeny. The pathophysiological significance of fusion events in cancer initiation and
progression, however, remains largely uncharacterized. In this project, we will analyze how cell-
cell fusion contributes to the pathogenesis of the malignant brain cancer astrocytoma. We
hypothesize that astrocytoma growth and progression from low-grade status to high-grade
glioblastoma (GBM) is driven, in part, by fusion between tumor cells and neural stem and
progenitor cells (NPs) in the brain microenvironment. We base this hypothesis on the following
unpublished experimental data presented in this application: (i) non-malignant NPs are recruited
to early stage astrocytomas and readily incorporate into the tumor cytoarchitecture; (ii) NPs and
astrocytoma cells can fuse to yield proliferative and poorly differentiated hybrid progeny with
stem-like properties; (iii) tumor growth and progression to GBM correlate with NP recruitment
and fusion with tumor cells; and (iv) human GBMs contain multinucleated cells that express NP
markers that may arise via cell-cell fusion. To analyze mechanisms of pathological cell fusion in
GBM we will generate and characterize a unique set of in vitro and in vivo systems. First,
genetic-based lineage tracing experiments will be used to purify cell fusion hybrids and study
self-renewal, multipotency, cytogenetic abnormalities and gene expression profiles. Second,
functional roles for cell fusion hybrids in tumor growth and progression will be studied using
transgenic pre-clinical mouse models of GBM. We will use genetic strategies to inhibit cell-cell
fusion or kill newly generated fusion hybrids in vivo and quantify astrocytoma growth, invasion
and progression to GBM. In summary, the experiments proposed in this project will reveal novel
roles for resident NPs in the brain microenvironment in driving tumor progression and molecular
genetic heterogeneity via cell-cell fusion.

## Key facts

- **NIH application ID:** 9849817
- **Project number:** 5R21NS103841-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Joseph H McCarty
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $200,000
- **Award type:** 5
- **Project period:** 2019-01-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849817

## Citation

> US National Institutes of Health, RePORTER application 9849817, Analyzing Cell-Cell Fusion in Glioblastoma Growth and Progression (5R21NS103841-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9849817. Licensed CC0.

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