# The role of granulocyte colony stimulating factor in metastatic colon cancer

> **NIH NIH P20** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2022 · $187,600

## Abstract

Primary colorectal cancers (CRC) demonstrate significant variability in expression of granulocyte colony
stimulating factor and receptor (GCSF/R), yet the effect of these varying levels of expression on the metastatic
potential of CRC is unknown. The long-term goal of this work is to discover and test new therapeutic targets for
CRC based on an improved understanding of the tumor microenvironment. The overall objective of this project
is to determine the extent to which elevated GCSF signaling increases metastasis in CRC, and to interrogate
the underlying causal mechanisms. The central hypothesis is that increased GCSF signaling promotes CRC
metastasis. The rationale for the proposed research is that an understanding of how GCSF signaling may
enhance CRC metastatic potential will lay critical groundwork for consideration of GCSF as a therapeutic target
for this lethal disease. Guided by strong preliminary data, this hypothesis will be tested by completing three
specific aims: (1) determine the extent to which serum GCSF levels and metastatic tumor expression of GCSF
and GCSFR correlate with outcomes in CRC patients with metastatic disease; (2) determine the extent to which
varying levels of GCSF and GCSFR expression enhance CRC metastasis in a cell-intrinsic manner; and (3)
determine the extent to which CRC GCSF signaling, systemic neutrophils, and tumor associated neutrophils
interact to augment CRC metastasis. Under Aim 1, two possible correlations will be assessed: (1) between
disease specific outcomes and GCSF levels in serum, and (2) between disease specific outcomes, and GCSF
and GCSFR levels within the tumor microenvironment. Lentiviral transduction, shRNA, and CRISPR technology
will be used in Aim 2 to modify human and murine CRC cells to over-express, downregulate, or abrogate both
the receptor and ligand. This will allow quantitative evaluation of the influence of expression level on cell-intrinsic
metastatic potential. Finally, in Aim 3, mouse models of micro- and macro-metastatic CRC will be used to
determine how CRC GCSF signaling affects neutrophils (both systemic and tumor microenvironment) and how
these interactions affect metastatic potential in vivo. This will extend the study beyond the clinical correlations
and in vitro work to provide insight into the role of CRC GCSF signaling in the complex environment of an intact
immune system. The approach is innovative, in the applicant's opinion, because it investigates a previously
unexamined link between a pro-inflammatory cytokine that is highly over-expressed in human CRC and the role
of tumor associated neutrophils in CRC using a combination of data from patients, as well as mechanistic in vitro
and in vivo work. The approach is significant because it is expected to advance the study of CRC by producing
a detailed understanding of the effects of a newly observed variation in human CRC. Specifically, the cell-intrinsic
and cell-extrinsic effects of variable GCSF and GCSFR expressio...

## Key facts

- **NIH application ID:** 10455520
- **Project number:** 5P20GM103639-10
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Katherine T Morris
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $187,600
- **Award type:** 5
- **Project period:** 2012-09-05 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455520

## Citation

> US National Institutes of Health, RePORTER application 10455520, The role of granulocyte colony stimulating factor in metastatic colon cancer (5P20GM103639-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10455520. Licensed CC0.

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