# Progastrin Modulates T-cell and Neutrophil Function to Modulate Colorectal Carcinoma Metastasis

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $75,858

## Abstract

ABSTRACT
Background: The progression of colorectal carcinoma (CRC) to metastasis is an inefficient process that
involves coordinated interactions between tumor and its immune microenvironment. We have found that a
CRC secreted peptide hormone, progastrin (PG), promotes CRC metastatic dissemination in an experimental
mouse model. Preliminary studies demonstrate that PG has a novel immune regulatory effect characterized by
increase systemic neutrophil accumulation and survival. PG's effect on neutrophils is indirect and requires
production of GM-CSF by T-cells.
Objective/Hypothesis: We hypothesize that the immune regulatory effect of PG creates a permissive
environment for metastasis. Hence, the main goal of this proposal is to understand PG's effect on the T-cells
and neutrophils that promote CRC metastatic dissemination in mouse models and in human disease.
Specific Aims:
 1. To establish the effect of progastrin in colorectal carcinoma metastasis and on T-cell and neutrophils
 2. To test the effect of progastrin on human immune cells and correlate progastrin expression in human
 colorectal carcinoma and metastasis
 3. Identify the T-cell subset that respond to progastrin and explore the underlying signaling mechanism
 4. To characterize the effect of progastrin on neutrophil function in the colorectal carcinoma tumor
microenvironment
Method: We will perform loss of function studies to establish the role of PG in CRC metastasis and further
investigate the role of T-cells in PG's effect on metastasis in vivo. We will measure the expression of PG in
CRC and metastasis from patient samples and correlate the findings with clinical outcome. We will identify the
T-cell subset(s) that produces GM-CSF and understand its signaling mechanism by genetic, molecular, and
biochemical approaches. We will characterize PG's effect on neutrophil functions and perform single-cell gene
expression studies of intratumoral neutrophils from patient CRC samples.
Cancer Relevance: Little is known about the how colorectal carcinoma regulates immunity to affect the
dissemination of CRC metastasis. We have identified a novel immune regulatory function of PG in CRC
metastasis and we aim to characterize its significance and mechanism, which may lead to new therapeutic or
preventive approaches against metastatic dissemination.

## Key facts

- **NIH application ID:** 9925186
- **Project number:** 5F32CA225144-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Su-Yang Liu
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $75,858
- **Award type:** 5
- **Project period:** 2018-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925186

## Citation

> US National Institutes of Health, RePORTER application 9925186, Progastrin Modulates T-cell and Neutrophil Function to Modulate Colorectal Carcinoma Metastasis (5F32CA225144-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9925186. Licensed CC0.

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