# Matrix stiffness mediated biglycan expression in the tumor vasculature

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2020 · $42,487

## Abstract

PROJECT SUMMARY
Angiogenesis refers to the process by which new blood vessels grow from pre-existing ones. Excessive
angiogenesis is a hallmark of many cancers and contributes to cancer progression. During tumor
growth, the angiogenic switch is deregulated resulting in an abnormal vasculature characterized by
hyperpermeable, tortuous, and immature blood vessels. Consequences of the irregular tumor
vasculature include poor tumor perfusion resulting in hypoxia and hindrance to therapeutic drug
delivery. While it is well established that chemical cues are heavily involved in regulating tumor
angiogenesis, the influence of mechanical cues are becoming more apparent. Notably, the extracellular
matrix is significantly stiffer than normal tissue in many cancers, and elevated matrix stiffness has been
shown to promote angiogenesis and disrupt barrier integrity. Prior work in our lab has shown both in
vitro and in vivo that increased matrix crosslinking (resulting in a stiffer matrix) increases endothelial
sprouting and causes more permeable blood vessels to form. However, the mechanisms governing the
effects of matrix stiffness on endothelial cell function are still poorly understood. Uncovering the
mechanisms driving stiffness-mediated effects on endothelial cells is critical for developing novel
approaches to normalize tumor vasculature and promote normal vessel growth. Interestingly, our
preliminary data obtained through RNA-sequencing indicate that endothelial biglycan expression is
regulated by matrix stiffness in vitro and in vivo. Previously, biglycan has been identified as a tumor
endothelial cell marker and biglycan overexpression is correlated to poor prognosis in several cancers.
Notably, biglycan can promote angiogenesis as an autocrine agent. While it is established that biglycan
is upregulated in disease and contributes to pathological endothelial signaling and behavior, our data
indicates that ECM stiffness may drive these effects. Given these findings, we will use tailored
biomaterials, transgenic mice, and state of the art biochemical assays to investigate the hypothesis that
matrix stiffness increases cellular contractility to drive elevated endothelial biglycan expression and
promote aberrant angiogenesis and hyperpermeability. In aim 1, the molecular mechanism governing
matrix stiffness driven endothelial biglycan expression will be determined. In aim 2, the effects of matrix
stiffness-mediated endothelial biglycan expression in promoting increased angiogenesis and a
hyperpermeable phenotype will be investigated. This work will provide critical insight into how the
mechanical properties of tumors regulate the structure and integrity of vasculature and uncover
potential therapeutic targets for vasculature normalization with a focus on endothelial biglycan
regulation.

## Key facts

- **NIH application ID:** 10068543
- **Project number:** 1F31HL154727-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Paul Taufalele
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $42,487
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10068543

## Citation

> US National Institutes of Health, RePORTER application 10068543, Matrix stiffness mediated biglycan expression in the tumor vasculature (1F31HL154727-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10068543. Licensed CC0.

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