# Mechanical properties of adipose tissue and its effect on breast cancer

> **NIH NIH R01** · CORNELL UNIVERSITY · 2024 · $507,847

## Abstract

PROJECT SUMMARY
We recently discovered an unexpected and intriguing role for white adipose tissue (WAT) in breast cancer. Our
past studies identified that the mechanical properties of WAT extracellular matrix (ECM) regulate tumor cell
invasion, a key rate-limiting step of metastasis, and that these properties are altered in obesity, contributing to
the increased prevalence and worse prognosis of breast cancer in obese patients. Now, recent preliminary data
from our labs additionally suggest that adipocyte mechanical properties may be similarly important. However,
how adipocyte mechanics change with obesity and which effect these changes have on ECM remodeling and
tumor invasion remains largely unclear. Understanding these connections is important for several reasons: First,
while the biochemical functions of WAT are widely known to contribute to the pathogenesis of breast cancer, the
influence of WAT mechanical properties on breast cancer invasion is largely unexplored. Second, our preliminary
data suggest that aberrant remodeling of WAT in obese individuals promotes breast cancer invasion due to
adipocyte lipid loss, transdifferentiation into myofibroblasts, and consequential changes in ECM deposition all of
which affect WAT mechanics. Last, our preliminary results also indicate that tumor-induced lipid loss may
synergistically promote invasion by changing WAT mechanical properties and tumor cell metabolism. Elucidating
how these parameters are interconnected will be critical to decrease breast cancer burden and requires
computational methods to uncover how single-cell properties of adipocytes and tumor cells affect WAT
mechanics and tumor cell invasion. Through three focused and complementary Specific Aims, the proposed
work iteratively couples computational models of tumor cell invasion into WAT, materials characterization of
adipocytes and ECM, engineered cell culture models, and transgenic mouse models that allow visualization and
manipulation of WAT in the mammary gland. Furthermore, single cell and spatial RNA transcriptomics, coupled
with advanced bioinformatics approaches and human specimens, will determine the associated molecular
mechanisms and potential value to patient prognosis. In particular, we will (1) define WAT physical properties in
the breast as a function of obesity and determine their effect on tumor invasion, (2) determine the synergistic
effect of tumor-induced lipid loss on WAT physical properties and tumor cell metabolism, and (3) establish the
molecular basis of tumor-induced lipid loss in lean versus obese adipocytes and determine their effect on WAT
physical properties and tumor invasion. These studies will identify specific obesity-dependent changes in WAT
mechanical properties and their associated molecular mechanisms that will help predict the risk of breast cancer
invasion for a given patient based on histological analysis.

## Key facts

- **NIH application ID:** 10928170
- **Project number:** 5R01CA276392-02
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Claudia Fischbach
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $507,847
- **Award type:** 5
- **Project period:** 2023-09-12 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10928170

## Citation

> US National Institutes of Health, RePORTER application 10928170, Mechanical properties of adipose tissue and its effect on breast cancer (5R01CA276392-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10928170. Licensed CC0.

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