Inhibition of Neutrophil Extracellular Traps with Chloroquine Reduces Peritoneal Metastatic Tumor Burdon

Pavan Rao, Brett Szeligo, B. Matthew Fagan, Abby D. Ivey, Pranav Murthy, David Brooks*, John Nasr, Carl R. Schmidt, Wallis Marsh, Brian A. Boone, MD
Health Science Center South, West Virginia University, Morgantown, WV, 26505

Presentation Category: Biological Sciences (Poster presentation)

Student’s Major: Biology

Introduction: Neutrophil extracellular traps, a process in which neutrophils release the contents of their DNA, histones, granules into the circulatory system. They are mainly responsible for eliminating microorganisms that enter the body, engulfing organisms through a specific cell death process, and even initiating certain immune cell responses. NET’s have been involved in the finding of metastatic disease, via progression of cells throughout the circulatory system and becoming the leading cause of death in cancer patients and have yet to have been studied on why. Therefore, NET’s can have a therapeutic target in the formation of metastatic disease and can lead to the prevention of peritoneal carcinomatosis. Methods: Intra-peritoneal injects of murine colon cells were given to 8-week-old Black 6 wildtype mice, and at random selection they were chosen to receive chloroquine or normal drinking water. After a 2-week period the mice were then sacrificed and assessed for their peritoneal tumors. Blood was obtained via cardiac puncture, and murine pancreatic cancer cells were also observed. Plasma Cell free DNA was taken and measured using Quan-iT PicoGreen assay. Results: Peritoneal Tumor burden was marked lyre reduced with the chloroquine treatment. Peritoneal tumor burden was similarly reduced with the chloroquine treated Pancreatic cancer tumor injected mice as well. Plasma cF DNA was lighter in chloroquine treated mice. This is consistent in inhibition of Neutrophil Extracellular Traps. Discussion: Chloroquine reduces peritoneal metastatic disease along with reducing the circulating cell-free DNA, a marker of NET formation. Finding these provide evidence of the role of NETs in metastatic diseases and highlight a therapeutic target to reduce this peritoneal disease formation. Conclusion: Neutrophil Extracellular traps are going to continue to promote peritoneal metastatic disease by erupting and releasing their contents into the circulatory system. This is no doubt. In the future, we’d like to administer DNase 1, a phosphodiester responsible for eliminating a strand of RNA, to further prevent the formation of NETs.

Funding: American Cancer Society Institutional Research Grant

Program/mechanism supporting research/creative efforts: WVU's Research Apprenticeship Program (RAP) & accompanying HONR 297-level course