# Biomechanical Regulation of Angiogenesis during Tumor Progression

> **NIH NIH R00** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $249,000

## Abstract

Project Summary
During cancer progression, angiogenesis is upregulated to supply the ever-increasing metabolic demands of
the growing tumor. While targeting tumor-associated angiogenesis has been a therapeutic strategy for many
years, these techniques demonstrate limited effectiveness in many cancer types. We believe this may be due
to limited understanding of the biomechanical environment of the tumor. Recently cancer-associated
fibroblasts (CAFs) have been shown to be key regulators of the peritumoral environment responsible for
secreting several growth factors that control angiogenesis and metastasis. CAFs exhibit a myofibroblast-like
phenotype, with increases in alpha-smooth muscle actin and Snail1. We hypothesized that CAF-generated
increases in biomechanical strains enhance tip cell activation and drive angiogenesis in the tumor
microenvironment. Our initial work has demonstrated that CAF biomechanical activity is directly related to the
vascularization potential of these cells in in vitro models of vascular growth, and that inhibiting the
mechanotransductive pathways in these cells abrogated their ability to support the formation of blood vessel
networks. Continuing this research will further elucidate the roles of biomechanics during tumor progression as
well as reveal potential targets for novel anti-cancer therapeutic strategies. During the K99 portion of the grant,
we will (1) investigate the role of CAF biomechanics in an in vivo angiogenic mouse model and (2) optimize a
microfluidic platform for angiogenesis studies that will allow for isolation and interrogation of biomechanical
parameters. The proposed microtissue platform will be highly innovative in that it allows for independent control
of several key biomechanical properties. Importantly, this phase of the grant will complement the PI’s career
development by incorporating training in cancer cell biology analysis techniques as well as mouse models of
cancer progression. During the R00 portion of the grant, we will investigate how endothelial cells respond to
mechanical cues from CAFs utilizing the microtissue model previously developed. Finally we will investigate
potential anti-cancer therapeutic strategies targeting CAF biomechanical promotion of tumor development in a
mouse model of breast cancer. Ultimately this work has significant implications for not only understanding
biomechanics of cancer progression but also the development of a unique in vitro microtissue model that will
permit interrogation of biomechanics in a truly original manner. The training, techniques, and approaches
developed during this grant should open several new avenues for future studies and will allow the PI to
transition into a fully-independent investigator.

## Key facts

- **NIH application ID:** 10139508
- **Project number:** 4R00CA230202-03
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Mary Kathryn Sewell-Loftin
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2018-08-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10139508

## Citation

> US National Institutes of Health, RePORTER application 10139508, Biomechanical Regulation of Angiogenesis during Tumor Progression (4R00CA230202-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10139508. Licensed CC0.

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