Determining the Mechanism Mediating the Upregulation of Chemokines by DHMs – UROP Spring Symposium 2021

Determining the Mechanism Mediating the Upregulation of Chemokines by DHMs

Mary Kritikos


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 3 (1pm-1:50pm)
Breakout Room: Room 17
Presenter: 4

Event Link


Neutrophils, which are immune system cells, express the chemokine receptor CXCR2. It has been shown that the ligands of CXCR2 are found at higher levels in triple negative breast cancer. In a previous study about the interaction between a tumor and the immune system, it was found that stimulated neutrophils may lyse – releasing a material made up of DNA/protein referred to as neutrophil extracellular traps (NETs). It was recently found that these NETs can promote tumor metastasis in triple negative breast cancer. Previously in our lab, a DNA-histone mesostructure (DHM) was created to mimic the functions of a NET. A DHM is a simplified version of a NET containing only DNA and histones. Metastatic 4T1 cells and non-metastatic 4T07 cells have a similar genetic background (being derived from the same parental tumor), yet in vitro, 4T1 cells have been shown to constitutively produce CXCR2 ligands while 4T07 cells do not. However, in the presence of a DHMs the two cell lines produce similar levels of CXCR2 ligands – possibly recapitulating aspects of the interaction between NETs and these tumor cells in vivo. In order to determine what the mechanism is for the difference in neutrophil infiltration between 4T1 and 4T07 tumors in vivo, we are looking at multiple genes involved in the expression of CXCR2 ligands to better understand the interaction between NETs and these tumors. In these experiments, we will be examining gene variants and changes in the activity of three signaling pathways: PDGF R beta, SCF R, and FLT-3.

Authors: Mary Kritikos, Priyan Weerappuli
Research Method: Qualitative Study

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