# Beige Adipocytes and African American Breast Tumors

> **NIH NIH SC1** · CHARLES R. DREW UNIVERSITY OF MED & SCI · 2020 · $358,750

## Abstract

African American (AA) women continue to suffer from high mortality rates from an aggressive
form of breast cancer for which there is no treatment. Better understanding of the unique
properties of AA tumor cells and the microenvironment that supports its growth might improve
clinical outcomes. Macrophages are a lynchpin in tumor microenvironment regulation. Although
high macrophage infiltration and increased angiogenesis are unique characteristics of AA breast
tumors, mechanisms that support these biological processes remain poorly understood. We have
recently demonstrated, for the first time that increase in beige/brown adipose phenotype promote
development of xenografts from breast cancer cells. We have subsequently demonstrated that
expression of beige markers is significantly increased in both xenografts obtained from AA triple-
negative (TN) breast cancer cells as well as in AA TN breast tumors. Based on our published and
preliminary data, we hypothesize that “cross-talk between tumor cells and beige adipocytes
generates a unique microenvironment that promotes M2 macrophage phenotype and is
conducive to high angiogenesis.” We will test our hypothesis with the following Specific Aims:
Aim 1: Determine whether i) M2 macrophages increase beige adipose phenotype in breast
cancer cells and ii) beige adipose cells crosstalk with tumor cells to increase aggressive behavior
in AA TN breast tumors. Aim 2: Determine the molecular mechanisms by which beige adipocytes
in AA breast tumors support and sustain M2 macrophage population. Aim 3: Determine whether
Th2 cytokines in AA TN breast tumor microenvironment promote proliferation and commitment of
bi-potent adipose precursors (AP) to beige lineage. Effect of depletion of tissue resident
macrophages and tyrosine hydroxylase (TH) expressed in these macrophages, on beige adipose
phenotype as well as tumor growth in-vivo will be analyzed. Co-culture experiments with
adipocytes enriched in beige phenotype and AA TN breast cancer cells will be performed to
elucidate mechanisms that support M2 macrophages/angiogenesis. We will examine the possible
role of psoriasin, and beige adipose-enriched secretory factors Neuregulin 4 (Nrg4) and Meteorin-
like (Metrnl) during the cross-talk between cancer cells and beige adipocytes. We will further
analyze the role of psoriasin in promoting MCSC (ALDH+)-induced xenograft growth.
Depletion/enrichment of breast tumor cells with adipose precursor PDGFRα cells will be examined
for tumor growth, beige adipose/M2 markers and tumor growth. Increased understanding of
detailed molecular mechanisms by which beige adipocytes sustain critical threshold of M2
macrophage population in tumor microenvironment and contribute to tumor progression may
provide outstanding opportunity for therapeutic intervention for these aggressive AA TN breast
tumors.

## Key facts

- **NIH application ID:** 9971487
- **Project number:** 5SC1CA232319-08
- **Recipient organization:** CHARLES R. DREW UNIVERSITY OF MED & SCI
- **Principal Investigator:** SHEHLA PERVIN
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $358,750
- **Award type:** 5
- **Project period:** 2018-07-06 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971487

## Citation

> US National Institutes of Health, RePORTER application 9971487, Beige Adipocytes and African American Breast Tumors (5SC1CA232319-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971487. Licensed CC0.

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