‘Sticky Webs of DNA’ in Pathogenesis of Ovarian Cancer
Posted: Wednesday, January 2, 2019
Ovarian cancer metastasis may be facilitated by webs of DNA extruded by neutrophils in the omentum, according to a preclinical study published by Honami Naora, PhD, of The University of Texas MD Anderson Cancer Center, and colleagues, in the Journal of Experimental Medicine. The authors reported that ovarian cancer cells can induce neutrophils to extrude chromatin fibers. Known as neutrophil extracellular traps, these webs of DNA normally capture invading microbes, but in the context of ovarian cancer, they may also capture malignant cells that colonize the omentum.
“Our findings support a model in which the influx of neutrophils and formation of [neutrophil extracellular traps] in the premetastatic omental niche promotes a microenvironment that is conducive for preferential implantation of ovarian cancer cells at this site,” wrote the authors.
In this study, syngeneic orthotopic mouse models were first used to evaluate tropism of injected luminescence-expressing ovarian cancer cells. The authors found that, after antibody staining, ovarian cancer cells preferentially formed implants within the omentum; within days (prior to colonization), neutrophils were recruited to vasculature-dense “milky spots.” When neutrophils were depleted, omental metastasis as well as cancer cell implantation were inhibited.
In a separate set of experiments, the authors found that neutrophils did indeed chemotax toward ovarian cancer cells and that factors from the latter induced extrusion of neutrophil DNA to form neutrophil extracellular traps. When formation of neutrophil extracellular traps was inhibited, omental colonization and metastasis decreased.
“Further studies of this intriguing host defense mechanism could yield new insights into improving ovarian cancer treatment and ameliorating common comorbidities,” the authors concluded.
Disclosure: The study authors reported no conflicts of interest.