# Evaluating How Fluid Shear Stress Alters Estrogen Receptor Phenotype in Metastatic Breast Cancer

> **NIH NIH R03** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2022 · $70,136

## Abstract

PROJECT SUMMARY
Approximately 70% of breast cancer patients will present with an estrogen receptor positive (ER+) subtype. Of
these patients, most will initially respond to endocrine therapy when treating the primary tumor. Unfortunately,
following metastatic spread, many of these patients develop a resistance to endocrine therapies which results in
a significant increase in patient mortality because there is no viable treatment for metastatic breast cancer.
Following metastasis, the current median survival time is ~5-10 years, which reinforces the critical need to better
understand the cellular mechanisms leading to endocrine therapy resistance in metastatic tumors. Endocrine
resistance at metastatic sites is hypothesized to occur through multiple mechanisms including: (i) loss of the
estrogen receptor, (ii) acquisition of additional mutations, and/or (iii) alterations in estrogen and growth factor
mediated signaling cascades. During metastasis, ER+ breast cancer cells are exposed to high magnitudes of
fluid shear stress (FSS) (up to 60 dyn/cm2) and fluid-induced deformation while traveling through the vasculature.
Prior work has identified that FSS induces an increased activation of kinase pathways, including those involved
in rapid estrogen signaling and associated endocrine resistance in cancer cell lines. Unfortunately, the role for
FSS on the regulation of ER signaling and the biological adaptation of ER+ breast cancer during metastasis is
not fully understood. To elucidate how FSS drives endocrine response in metastatic breast cancer, we propose
the following hypothesis: Exposure of ER+ breast cancer cells to FSS represses ER expression and induces
activation of growth factor signaling cascades and subsequent endocrine resistance. We propose to test this
hypothesis utilizing a modular microfluidic platform capable of exposing breast cancer cells to well-controlled,
uniform magnitudes and durations of FSS that mimics in situ conditions that occur during metastatic spread.
Specifically, we will (1) Determine how FSS alters estrogen receptor expression and growth factor pathways that
interact with estrogen signaling cascades, and (2) Evaluate the effects of FSS on the acquired resistance to
endocrine therapy. A hallmark of the proposed technology is the ability to perform both bulk off-chip interrogation
and cellular selection and on-chip single cell analysis using fluorescent microscopy to characterize the
heterogeneous nature and response of individual cancer cells. These studies will provide new fundamental
insight into the effects of FSS on estrogen signaling to identify novel mechanisms of endocrine resistance in ER+
breast cancer at metastatic sites, this has the potential to lead to novel therapies designed to treat metastatic
ER+ breast cancer.

## Key facts

- **NIH application ID:** 10451678
- **Project number:** 5R03CA262944-02
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** WILLIAM T MONROE
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $70,136
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10451678

## Citation

> US National Institutes of Health, RePORTER application 10451678, Evaluating How Fluid Shear Stress Alters Estrogen Receptor Phenotype in Metastatic Breast Cancer (5R03CA262944-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10451678. Licensed CC0.

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