Macrophage polarization: Role of PPARγ activation in chronic inflammation-associated breast cancer

8^th International Conference and Exhibition on Metabolomics & Systems Biology

May 08-10, 2017 Singapore

Shreya Kar

National University of Singapore, Singapore

Posters & Accepted Abstracts: Metabolomics

Abstract :

The tumor microenvironment is a complex architecture in which the functionally diverse and the heterogeneous macrophages play an important role in tumor growth and metastasis. Macrophages exhibit cellular plasticity and have various subtypes with distinct phenotypic properties depending on the micro environmental "signals". Peroxisome proliferator-activated receptor gamma (PPAR�³) is a ligand-activated transcription factor expressed in macrophages and has been shown to promote macrophages to alternatively activated M2 phenotype in various cancers. This is responsible for immunosuppression and tumor growth. However, its effect on macrophage polarization in chronic inflammation-associated breast cancer is not fully understood. Herein, by using murine macrophages and a panel of breast cancer cell lines, we show exposure of macrophages to conditioned media from metastatic breast cancer cell lines prime them to adopt an M2 phenotype with dose-dependent increase in PPAR�³ expression along with M2 markers. Conversely, inhibition of PPAR�³ activity reverses this phenotype. Interestingly, treatment of macrophages with PPAR�³ activators that belong to the drug class of thiazolidinediones (TZDs) enhanced the M2 phenotype which was effectively blocked when used together with a PPAR�³-specific antagonist. Therefore, exploring the role of PPAR�³ in the dynamic process of macrophage polarization and the mechanisms governing this process not only is important for our understanding of the M1â��M2 paradigm of macrophage polarization but also provides insights to new treatment strategies via targeting imbalances of macrophage polarization. Moreover, a newer and safer molecule that activates PPAR�³ is much needed in the clinic as the TZDs do have toxic side effects. To that effect, we have recently set up a collaboration agreement with pharmaceutical company, Daiichi Sankyo USA, for the use of their pipeline Phase II-completed PPAR�³ activator, CS-7017, in our subsequent studies.

Biography :

Email: shreya.kar@u.nus.edu