# Adhesive regulation during cell migration

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $362,722

## Abstract

ABSTRACT
Cell migration is important in normal development, wound healing and cancer. The long-term
goal of this work is to study cell migration in the context of cancer. The most motile, and
understudied, population of cells in the tumor microenvironment (TME) are neutrophils, which are
primary effector cells of the innate immune response. The presence of chronic neutrophil-
mediated inflammation has been associated with the initiation and progression of cancer.
However, the role of neutrophils in the tumor microenvironment remains controversial in part
because neutrophils can play both pro- and anti-tumor roles. We aim to address this gap by
increasing our understanding of how neutrophils are recruited and regulated by the tumor
microenvironment during tumor progression. We will test the overall hypotheses that specific
signaling pathways induced by transformed cells drive neutrophil recruitment, and that
neutrophils “educated” in the tumor microenvironment alter tumor progression. To
address these hypotheses, we have developed a robust toolbox using zebrafish to enable in situ
imaging of the dynamic behavior of neutrophils, macrophages and cancer cells, in real time, in
melanoma and liver cancer models. We take advantage of a new zebrafish model of fibrolamellar
carcinoma (FLC), an aggressive early onset cancer that exhibits increased inflammation and early
progression, similar to human disease. Here, we propose to examine the role of neutrophils in
liver cancer and melanoma inflammation and progression (Aim 1). We will harness TRAPseq
findings from neutrophils, macrophages and epithelial cells to probe the role of oncogene-induced
genes on neutrophils in the tumor microenvironment and tumorigenesis, including the role of
neutrophil intrinsic genes p47phox and the phosphatase ptprja on neutrophil polarization and
tumor progression (Aim 2). Finally, we will examine neutrophil-macrophage cross talk in the tumor
microenvironment and the role of macrophage polarization on neutrophil inflammation and tumor
progression (Aim 3). While there has been substantial interest in manipulating the adaptive
immune system to treat cancer, the therapeutic possibilities of the innate immune system remain
under-studied. Understanding mechanisms that regulate neutrophils in the tumor
microenvironment will enhance basic mechanistic knowledge regarding intercellular interactions,
facilitate the design of new strategies to treat cancer and potentially improve the efficacy of cancer
immunotherapy.

## Key facts

- **NIH application ID:** 10356648
- **Project number:** 2R01CA085862-21A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Anna Huttenlocher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $362,722
- **Award type:** 2
- **Project period:** 2000-06-10 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356648

## Citation

> US National Institutes of Health, RePORTER application 10356648, Adhesive regulation during cell migration (2R01CA085862-21A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10356648. Licensed CC0.

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