# Contributions of FGFR-mediated tumor-stromal interactions to breast cancer growth and progression

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $352,275

## Abstract

PROJECT SUMMARY
Breast cancer growth and progression require complex interactions between tumor cells and their surrounding
environment. Understanding the key tumor-stromal interactions that drive breast cancer growth and metastasis
is critical for the development of strategies to inhibit tumor progression and recurrence. Breast cancers are
often associated with an inflammatory environment, which has been linked to enhanced breast cancer
progression. The availability of anti-inflammatory agents for clinical use enhances the feasibility of targeting the
inflammatory microenvironment. However, understanding the mechanisms that drive the formation of an
inflammatory environment and identifying key mediators that contribute to breast cancer growth and
progression are critical for developing successful anti-inflammatory therapeutic strategies. Fibroblast growth
factors (FGFs) are well-established promoters of cancer growth and progression. Collectively, FGFs and their
receptors (FGFRs) are overexpressed and/or amplified in up to 75% of human breast cancers and increased
FGFR activity is correlated with poor patient outcome. We have recently found that FGFR activation leads to
pro-tumorigenic alterations within the extracellular matrix (ECM) including enhanced synthesis and
fragmentation of the ECM component hyaluronan. Furthermore, we have identified a novel pathway activated
by hyaluronan in breast cancer cells along with pro-inflammatory mediators that contribute to hyaluronan
function. These studies have led to the hypothesis that activation of FGFR in breast cancer cells leads to the
formation of an HA-rich inflammatory microenvironment, which promotes tumor growth and progression by
activating pro-inflammatory signaling pathways and promoting expression of inflammatory mediators. The
following specific aims are proposed: 1) Determine the functional contributions of FGFR-mediated HA
synthesis and fragmentation to mammary tumor progression. 2) Delineate the specific signaling pathway
through which HA regulates inflammatory gene expression in breast cancer cells. 3) Develop combination
therapies that target FGFR and downstream HA effectors. The significance of these studies is that they will
define novel interactions between tumor cells and the ECM. A major goal of these studies is to determine the
ability of combination therapies that target both tumor cells and HA: receptor interactions in the
microenvironment to limit tumor initiation and growth.

## Key facts

- **NIH application ID:** 9894751
- **Project number:** 5R01CA215052-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Kathryn L Schwertfeger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,275
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894751

## Citation

> US National Institutes of Health, RePORTER application 9894751, Contributions of FGFR-mediated tumor-stromal interactions to breast cancer growth and progression (5R01CA215052-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9894751. Licensed CC0.

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