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 10
Triple negative breast cancer (TNBC) is a type of breast cancer that is defined by the absence of estrogen receptors, progesterone receptors, and the low expression of HER2. The combined absence of these markers, historically, led to TNBCs having poorer prognosis due to the lack of therapeutic targets. Recent research reported by the Egeblad group (Cold Spring Harbor Laboratory) was able to identify that neutrophil extracellular traps (NETs), a pathogen trapping structure comprised of DNA, histones, and various other neutrophil-associated proteins, typically produced in the presence of a pathogenic infection, are prompted to form by metastatic breast cancer cells in the absence of an active infection. By studying the effect of inhibiting neutrophil infiltration, NET production, and of breaking down NETs within a short time through the use of DNase I treatment in vivo; the Egeblad group demonstrated that metastasis of the traditionally-metastatic 4T1 cell line could be prevented/delayed simply by targeting the interaction between tumors and NETs – thereby establishing NETs as a potential therapeutic target for the treatment of TNBC. Using the same 4T1 and 4T07 cell lines examined by the Egeblad group, we have recently demonstrated that these two cell lines constitutively produce different levels of CXCR-2 ligands in vitro when grown in control/untreated conditions; but produce similar levels when cultured in the presence of a NET-like biomaterial we have developed that we refer to as DNA-histone mesostructures (DHMs). Because 4T1 and 4T07 cells are derived from the same spontaneously-occurring parental tumor, this difference in constitutive expression poses interesting questions: what mutational differences may be present in 4T1 cells (but not in the 4T07 cells) that contributes to their constitutive production of CXCR-2 ligands (which act as neutrophil chemoattractants and induce the production of NETs by infiltrating neutrophils), and what similarities exist between these cells that may underlie their shared response to DHMs in vitro. To address these questions, we have chosen to take a multi-faceted approach that examines transcriptomic data from 4T1 and 4T07 cells grown in vitro (+/- DHMs) and in vivo (+/- DHMs), conducting comprehensive literature reviews on cancer-related intracellular signaling pathways to see what genes and intracellular factors may shed light upon the source of the intrinsic difference between these cell lines.