# Shaping the Microenvironment by DPEP1 Facilitates Adenoma Progression

> **NIH NIH U54** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $603,822

## Abstract

PROJECT SUMMARY/ABSTRACT
Project 1: Shaping the Microenvironment by DPEP1 Facilitates Adenoma Progression
Project 1 aims to examine how shaping the microenvironment by DPEP1 facilitates adenoma progression. This
will be a basic project. We propose that dipeptidase-1 (DPEP1) marks those adenomas with the potential to
progress to colorectal cancer (CRC) through an active bi-directional communication with neutrophils. DPEP1
has two functions: dipeptidase activity and recently identified neutrophil-binding activity. Our hypothesis is that
DPEP1, largely through its neutrophil-binding activity, marks adenomas with a predilection for progression. We
have found that DPEP1 immunoreactivity is detected in 27% of colorectal adenomas but this increases to 72%
of CRCs, consistent with DPEP1 marking the small subset of adenomas that progress to CRC. Utilizing human
specimens, a unique Transwell co-culture system of adenoma organoids and freshly isolated neutrophils isolated
from healthy volunteers, and an informative mouse model, we will test if DPEP1-expressing adenomas more
effectively communicate with neutrophils and create a neutrophil-enriched microenvironment, increasing the
likelihood that these adenomas will progress. Exosomes have attracted a great deal of recent attention as a rich
source of cargo that may serve as cancer biomarkers. We have found that DPEP1 is released in exosomes from
CRC cell lines and that it highly enriched in a subset of exosomes that contain known CRC biomarkers, CEA
and EPCAM. Of interest, neutrophils also release small extracellular vesicles (sEVs) that contain neutrophil
elastase in a form that cannot be inhibited by elastase inhibitors, and thus it is especially potent in degrading the
extracellular matrix, a key step in cancer invasion. We will also use a unique neutrophil reporter mouse to monitor
onset and perdurance of neutrophil infiltration, along with the properties of these neutrophils, in an inducible,
stem cell-driven mouse model of colonic adenomas.
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## Key facts

- **NIH application ID:** 10926861
- **Project number:** 5U54CA274367-03
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Robert J. Coffey
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $603,822
- **Award type:** 5
- **Project period:** 2022-09-15 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10926861

## Citation

> US National Institutes of Health, RePORTER application 10926861, Shaping the Microenvironment by DPEP1 Facilitates Adenoma Progression (5U54CA274367-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10926861. Licensed CC0.

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