# SR-A as a therapeutic target in breast cancer

> **NIH NIH R21** · UNIV OF ARKANSAS FOR MED SCIS · 2024 · $214,583

## Abstract

ABSTRACT
Tumor-associated macrophages are critical regulators of tumor development, progression, and metastasis.
Factors in the tumor microenvironment induce tumor-associated macrophages to adopt a tumor-supportive
phenotype that suppresses immune responses. The accumulation of tumor-supportive macrophages in tumors
is associated with accelerated tumor progression and a poor patient prognosis. Macrophages sense and respond
to their environment by expressing pattern-recognition receptors such as Class-A Scavenger Receptors (SR-A).
In preliminary data, we show that SR-A binds to glycans expressed on breast cancer cells but not on non-cancer
cells. Furthermore, we show that SR-A expression promotes the development of palpable tumors and lung
metastases in mouse models that spontaneously develop breast cancer. Importantly, results from gene
expression profiling indicate that tumor-associated macrophages adopt an immune-suppressive phenotype in
SR-A-expressing mice but not in SR-A knock-out mice. These findings support the novel conclusion that SR-A
binding to tumor-specific ligands induces the polarization of tumor-infiltrating macrophages toward an immune-
suppressive phenotype that enhances breast cancer growth and metastases. It logically follows that inhibiting
SR-A interactions in tumors may provide an innovative approach that repolarizes TAMs to an antitumor
phenotype, improves the effectiveness of anti-tumor immune response, and inhibits breast cancer progression.
Thus, the goals of the proposed experiments are to i) identify the ligands on breast cancer cells that bind SR-A
and induce macrophage polarization toward a protumor phenotype, and ii) demonstrate that antagonizing SR-A
repolarizes macrophages toward a tumor-inhibitory phenotype, enhances the immune response, and prolongs
survival in preclinical models of breast cancer. Showing that antagonizing SR-A interactions increases anti-tumor
immune activity and prolongs survival in animal models will confirm the therapeutic potential of this approach to
treat breast cancer. In addition, identifying tumor-associated ligands that interact with SR-A may suggest
additional tumor-specific strategies for inhibiting these interactions.

## Key facts

- **NIH application ID:** 10784996
- **Project number:** 1R21CA280448-01A1
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Behjatolah Monzavi Karbassi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $214,583
- **Award type:** 1
- **Project period:** 2024-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10784996

## Citation

> US National Institutes of Health, RePORTER application 10784996, SR-A as a therapeutic target in breast cancer (1R21CA280448-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10784996. Licensed CC0.

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