Role of Wnt5a in Switching Macrophage Phenotype in the Tumor Microenvironment

Abstract

In 2018, cancer was the second leading cause of death in the United States. Past research has demonstrated the importance of macrophages in both the tumor microenvironment and in cancer progression. Macrophages are specialized immune cells that are differentiated into either the M1 phenotype (pro‐inflammatory/tumor‐suppressing) or M2 phenotype (anti‐inflammatory/tumor‐promoting), depending on the signals in the tumor microenvironment. Research has demonstrated that the expression of Wnt5a, a secreted glycoprotein, is correlated with a cancer’s level of aggression. Additionally, evidence shows that the treatment of M1 macrophages with Wnt5a increased the expression of IL‐10, a molecule expressed by M2 macrophages and associated with the progression of cancer. The objective of this study is to investigate the effect of exogenous Wnt5a on the expression levels of M1/M2 phenotypic markers. The hypothesis is that Wnt5a facilitates the switching of macrophages from the M1 to M2 phenotype through the induction of IL‐10. This would support the idea that Wnt5a functions as a tumor promoter and potentially contribute in the progression of cancer.To test this hypothesis, THP‐1 and human peripheral blood monocyte derived macrophages were evaluated for expression of the M1 markers CD80 and IL‐6 and the M2 markers CD163 and IL‐10 using flow cytometry and RT‐qPCR either with or without Wnt5a treatment.Our preliminary results confirm that, without Wnt5a treatment, M1 macrophages strongly expressed Wnt5a and, further, demonstrate that, after treatment with exogenous recombinant Wnt5a, the expression of M2 markers, including IL‐10, increased, while the expression of M1 markers decreased. Results from this study lead us to speculate that Wnt5a could play a role in switching macrophage phenotype from M1 to M2 and thus determining the overall tumor behavior. Furthermore, the manipulation of Wnt5a signaling could potentially be an attractive strategy in the development of more effective cancer treatments.Support or Funding InformationThe John J. Kopchick MCB/TBS Undergraduate Student Support Fund (Ohio University) andThe Provost Undergraduate Research Fund (Ohio University)