# Glioblastoma stem cell-derived pericytes and cancer invasion

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $346,719

## Abstract

Summary
Glioblastoma (GBM) is the most lethal primary brain cancer that is highly invasive and resistant
to current treatments. Cancer invasion and tumor recurrence are universal in GBM patients
despite maximal therapy. Some treatments such as anti-angiogenic regimens actually transform
tumor growth towards a more invasive phenotype. Defining the mechanisms underlying the
therapy-induced cancer invasion and tumor repopulation may help improve GBM treatment.
GBMs contain abundant vessels consisting of endothelial cells (ECs) and pericytes. Pericytes
play critical roles in maintaining vascular function and blood-brain (tumor) barriers. We found
that the majority of vascular pericytes in GBMs are derived from glioma stem cells (GSCs), a
highly plastic cellular subpopulation functionally defined by self-renewal, multipotency and tumor
propagation. Selective targeting of GSC-derived pericytes disrupted tumor vessels and potently
inhibited tumor growth, indicating that GSC-derived pericytes play crucial roles in supporting
vascular structure and function to promote tumor growth. In addition, GSC-derived pericytes
were detected on a subset of vessels in peritumoral brain, suggesting that these neoplastic
pericytes have the capacity to migrate into brain tissues. Our recent study using cell lineage
tracing demonstrated that GSC-derived pericytes have the potential to de-differentiate into
GSCs that are able to grow tumors. Moreover, GSC-derived pericytes are highly resistant to
current treatments, indicating that GSC-derived pericytes may function as a reservoir of tumor-
initiating cells to promote cancer invasion and tumor recurrence by de-differentiating into GSCs
after therapy. Thus, we hypothesize that GSC-derived pericytes are reserve cancer cells that
contribute to the therapy-induced cancer invasion and tumor recurrence and targeting
these neoplastic pericytes synergizes with current GBM treatments. We plan to test our
hypothesis by pursuing three specific aims: 1. Determine roles of GSC-derived pericytes in the
therapy-induced cancer invasion and tumor recurrence. 2. Define the molecular mechanisms
driving de-differentiation of GSC-derived pericytes into GSCs. 3. Determine whether targeting
GSC-derived pericytes synergizes with current GBM therapies. We will use in vivo cell lineage
tracing, selective targeting and other new techniques to elucidate the roles of GSC-derived
pericytes in the therapy-induced cancer progression and evaluate the synergistic impact of
targeting GSC-derived pericytes with current therapies in a preclinical setting. The proposed
studies will lay a solid foundation for the development of effective therapeutics or new treatment
combinations to significantly improve survival of GBM patients.

## Key facts

- **NIH application ID:** 9926320
- **Project number:** 5R01NS091080-05
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Shideng Bao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $346,719
- **Award type:** 5
- **Project period:** 2016-07-15 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9926320

## Citation

> US National Institutes of Health, RePORTER application 9926320, Glioblastoma stem cell-derived pericytes and cancer invasion (5R01NS091080-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9926320. Licensed CC0.

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