BME Spring Seminar: The Collagen-Dense Tumor Microenvironment Drives Inflammatory Signaling and Tumor Progression
April 2 @ 12:00 pm - 1:00 pm
Suzanne Ponik, Ph.D.;
Senior Scientist in the Department of Cell and Regenerative Biology in the School of Medicine and Public Health; University of Wisconsin-Madison
High breast density is linked to an increased risk of breast cancer, and correlates with changes in collagen organization. In a transgenic mouse model of collagen-dense mammary tumors there is accelerated mammary tumor formation and progression, increased recruitment of macrophages and neutrophils, and an overall increase in inflammatory cytokine signaling. However, the mechanisms by which collagen-dense tumors enhance inflammation and tumor progression remain poorly understood.
The use of multiple approaches to target inflammation in the collagen-dense tumor microenvironment have identified an important role for both neutrophils and signaling through Cyclooxygenase-2 (Cox-2), a key enzyme in prostaglandin metabolism. In separate studies the depletion of neutrophils and inhibition of Cox-2 signaling significantly impacted tumor growth and metastasis in collagen-dense tumors and had little effect on WT tumors. These findings demonstrate a clear role for Cox-2 induced inflammation and neutrophils to module tumor progression within collagen-dense microenvironments, and suggest that inhibition of COX-2 may be an effective therapeutic target for women with dense breast cancer.