# Defining the contributions of Lyve-1 expressing macrophages to breast cancer growth and progression

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2022 · $414,689

## Abstract

PROJECT SUMMARY
Breast cancer growth and progression require complex interactions between tumor cells and their
surrounding environment. Increased numbers of infiltrating inflammatory cells, in particular macrophages,
correlate with poor patient prognosis in breast cancer. Our studies have focused on identifying key
macrophage subpopulations that contribute to mammary tumor growth and progression. Based on studies in
the normal mammary gland, we have identified a stromal macrophage population that is associated with
remodeling hyaluronan in the extracellular matrix and is capable of promoting tumor cell invasion. These
macrophages are localized specifically to hyaluronan-enriched regions in the peri-tumoral stroma. Based on
our preliminary results, we hypothesize that this macrophage subpopulation represents a distinct tissue
resident-derived tumor associated macrophage population that contributes to breast cancer progression
through binding to and remodeling the hyaluronan-containing extracellular matrix. Studies proposed in
Specific Aim 1 will define the localization and source of this macrophage subpopulation using mouse models
of breast cancer. Studies proposed in Specific Aim 2 will delineate the key mechanisms through which these
macrophages contribute to extracellular matrix remodeling and drive tumor cell invasion. Finally, studies
proposed in Specific Aim 3 will define the localization of this macrophage subpopulation in human breast
cancers and use spatial transcriptomics to identify the local environment surrounding these macrophages.
Recent studies have highlighted the extensive functional diversity of macrophages in both normal
homeostasis and in various diseases, including cancer. Delineating the specific mechanisms that contribute
to macrophage heterogeneity and defining their functional contributions within the tumor microenvironment
are critical for developing strategies to effectively target this diverse population of cells.

## Key facts

- **NIH application ID:** 10467174
- **Project number:** 1R01CA265004-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Kathryn L Schwertfeger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $414,689
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10467174

## Citation

> US National Institutes of Health, RePORTER application 10467174, Defining the contributions of Lyve-1 expressing macrophages to breast cancer growth and progression (1R01CA265004-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10467174. Licensed CC0.

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