# Tissue-Engineered Models of Glioblastoma for Evaluating Treatment Response

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2022 · $519,881

## Abstract

Glioblastoma (GBM) is a uniformly fatal brain cancer with poor response to treatment and virtually inevitable
recurrence. GBM tumors do not metastasize. Instead, they aggressively infiltrate the brain. Tumor borders are
highly vascularized by microvessels that serve as key niche environments promoting GBM cell survival,
treatment resistance and migration. Currently, it is believed that a subpopulation of treatment-resistant, stem-
like GBM cells (GSCs) migrate away from primary tumors — remaining in close contact with local microvessels
— and seed recurrent tumors — which are enriched in GSCs. However, the mechanisms underlying the influence
of the microvessel niche on GBM cell migration away from primary tumors, leading to recurrence, remain largely
unknown. To address this gap in knowledge, the proposed studies will investigate 1) the role of specific cues in
the tumor microenvironment on the migratory phenotype of GBM cells and 2) how these cues differentially affect
distinct subpopulations of cells within heterogeneous tumors, including GSCs. Our fundamental hypothesis is
that the microenvironment surrounding tumor microvessels promotes GBM progression through both mechanical
and chemical means. Aim 1 will investigate effects of mechanical cues and Aim 2 effects of biochemical cues
present in the microvessel niche on migratory phenotype of GBM. To do this, we will use an innovative, tissue-
engineered platform for 3D culture of patient-derived GBM cells to quantify how specific features of the
microenvironment affect migratory behavior. We propose to modularly tune mechanical and chemical properties
of culture platforms to characterize their independent effects on migratory phenotype of GBM. For some
experiments, platforms will be constructed with an interface between defined microenvironments through which
GBM cells can migrate, enabling separation of migratory and non-migratory cells for downstream analysis and
providing information about how subpopulations of cells within a single tumor, such as GSCs, may respond
differentially to microenvironmental cues. As treatment resistance, invasion and recurrence are inter-related
events, we will investigate how exposure to routine clinical therapies may alter migratory responses of GBM to
microenvironmental cues. Using single-cell RNA sequencing, we will investigate the mechanisms underlying
responses to specific features of the microvessel niche. Collectively, the proposed studies will make significant
strides towards our understanding of how interactions of GBM with the microvessel niche promote tumor
recurrence by characterizing: 1) biomechanical properties of GBM tumors and microvessels (Aim 1), 2) migratory
response of GBM cells to biochemical and biomechanical cues (Aims 1 and 2) and 3) mechanisms governing
the migratory responses to biochemical and biomechanical cues (Aims 1 and 2). In the long term, we expect
these insights will lead to the development of new therapies targeting GBM recurre...

## Key facts

- **NIH application ID:** 10579031
- **Project number:** 7R01CA241927-04
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Stephanie Kristin Seidlits
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $519,881
- **Award type:** 7
- **Project period:** 2020-02-13 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10579031

## Citation

> US National Institutes of Health, RePORTER application 10579031, Tissue-Engineered Models of Glioblastoma for Evaluating Treatment Response (7R01CA241927-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10579031. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*