Investigating How the Presence of Neutrophils Impacts Tumor Metastasis – UROP Spring Symposium 2021

Investigating How the Presence of Neutrophils Impacts Tumor Metastasis

Madilyn Gaydos


Pronouns: She/Her

Research Mentor(s): Priyan Weerappuli, Postdoctoral Scholar
Research Mentor School/College/Department: Biological and Material Sciences, School of Dentistry
Presentation Date: Thursday, April 22, 2021
Session: Session 1 (10am-10:50am)
Breakout Room: Room 7
Presenter: 6

Event Link


This research is dedicated to learning about the role of neutrophils in the immune system and how they are involved in the disease progression of different cancers. 4T1 and 4T07 cell lines both originated within the same primary tumor, however, 4T7 is metastatic and the 4T07 cell line is not. When cultured in the presence of DHMs, both cell lines behave similarly which means that when NETs are absent (in vivo), the 4T1 cell line stops metastasizing.This suggests that the interaction between 4T1 cells and NETs is important for the metastasis of these tumors. We found that when cultured in vitro, 4T1 cells constitutively express/produce neutrophil chemoattractants (CXCR1 and CXCR2) while 4T07 cells do not, and when cultured in the presence of DHMs, both cell lines begin expressing/producing roughly equivalent, high levels of these chemokines. This has led us to hypothesize that there may be a feedback loop that underlies 4T1 metastasis where the constitutive expression of neutrophil chemoattractants leads to neutrophil infiltration of these tumors and the concomitant deposition of NETs. The interaction between NETs and the 4T1 cells, then, leads to the increased production of neutrophil chemoattractants and additional neutrophil infiltration. We predict that the 4T07 cells may be capable of metastasizing if they are exposed to the same neutrophil/NET-heavy microenvironment that develops within the 4T1 tumors; but because the 4T07 cells do not constitutively express neutrophil chemoattractants, this feedback loop is never initiated in these tumors. By comparing Genomic Transcriptomic Data for 4T1 and 4T07 Cell Lines, we found 39 mutations that are either present in one or both cell lines. Of these 39 mutations, I specifically researched the functions of M-CSF R, c-Ret, Tie-1, and Tie-2. In the future, I will research and determine what the functions of these gene products are and what signaling pathways would be disrupted by this mutation. Once all 39 mutated genes are analyzed, we will prioritize candidate genes to examine in vitro by identifying genes that are directly involved in the production of CXCR-2 ligands, feedback loops/signaling pathways that module inflammation, and endocytosis/macropinocytosis. The goal is to replace mutant alleles in 4T07 cells with corresponding alleles identified in 4T1 cells.

Authors: Madilyn Gaydos, Priyan Weerappuli
Research Method: Qualitative Study

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