# Functional Consequences of Racially Associated Ephrin Alterations on the Prostate Tumor Microenvironment

> **NIH NIH R01** · LOUISIANA STATE UNIV HSC SHREVEPORT · 2022 · $212,472

## Abstract

Project Summary
Prostate cancer (PCa) incidence and mortality remain significantly higher in African American (AA) men
compared to Caucasians (CA). Although socioeconomic factors may contribute to such differences, recent
studies suggest that biological factors could potentially explain racial disparities (RD) in PCa. A few high-
penetrance genes (HPG) have been found to predispose to high risk of PCa in AA men. These include EphB2
mutations. EphB2 is a tyrosine kinase (RTK) receptor that binds to the Ephrin ligand and initiates bidirectional
signals that affect both receptor (forward signaling) and Ephrin-expressing cells (reverse signaling). Our
preliminary observations suggest a potential supportive role of Ephrin signaling activation within stromal cells in
the tumor microenvironment (TME) due to the pathogenicity of these EphB2 genetic alterations. However the
functional consequences of EphB2 alterations on prostate cancer cell biology have not been experimentally
validated. To better understand the intrinsic mechanism(s) responsible for these pathogenic effects we
hypothesize that EphB2 alterations commonly seen in AA men may induce aberrant “forward signaling”
reducing its tumor suppressor function in cancer cells and abnormal “reverse signaling” increasing the
activation of stromal in the TME, overall resulting in support for PCa progression. This proposal seeks to
understand the downstream molecular effectors of disrupted Eph-Ephrin signaling in AA men in both tissue
compartments (epithelium and stroma) on PCa progression.
The long-term goal is to identify novel targetable molecules within the cancer and/or stromal compartment
that can be used to improve diagnosis and treatment of patients at high-risk of developing aggressive PCa
disease in AA men.
Three complementary areas will be investigated:
1. Determine the functional effects of racial EphB2 alterations on PCa progression. We will study the
functional consequence of common EphB2 alterations seen in AA men with PCa, on proliferation and motility
of PCa cells in vitro and in vivo. The role of EphB2 in PCa cell biology is unknown.
2. Determine the role of Ephrin reverse signaling on CAF activation in the TME of AA men. We
observed increased expression of EphB2 ligands in the TME of AA compared to CA men suggesting a
dysfunctional regulation of Ephrin-reverse signaling. In addition we observed that prostate stromal cell from AA
patients with PCa induce increased proliferation and motility of PCa cell lines in vitro and in vivo.
3. Evaluate the utility of targeting the Eph-Ephrin signaling to inhibit PCa progression. It has been
shown in experimental models that normalizing Eph-Ephrin signaling can reduce colon cancer progression.
The utility in PCa has not been previously studied. Using an in vivo PCa model, we will assess the feasibility of
targeting Eph-Ephrin signaling frequently altered in AA men to inhibit PCa tumorigenesis.

## Key facts

- **NIH application ID:** 10831717
- **Project number:** 7R01CA242920-05
- **Recipient organization:** LOUISIANA STATE UNIV HSC SHREVEPORT
- **Principal Investigator:** Omar Franco Coronel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $212,472
- **Award type:** 7
- **Project period:** 2019-07-03 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831717

## Citation

> US National Institutes of Health, RePORTER application 10831717, Functional Consequences of Racially Associated Ephrin Alterations on the Prostate Tumor Microenvironment (7R01CA242920-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10831717. Licensed CC0.

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