M2-macrophage derived exosomes mediates tumor progression via GATA3-IL-4-IL-13 axis in ovarian cancer

Tumor microenvironment is the key factor for tumor progression. Stromal cells which consist of, tumor associated macrophages(TAMs), tumor associated fibroblast as well as cancer stem cells has been implicated in the acquisition of oncogenic phenotype via cell-cell communication. Exosomes are the major players in tumor microenvironment that contributes to tumorigenesis. Exosomes carry genetic information from host cells to another cell to reprogram the recipient cell. Exosomes from TAMS has emerged as important mediators of tumor growth. Here, we report that GATA3 is released abundantly from TAM cells via exosomes and promote oncogenesis. GATA3 acts as an oncogenic protein and silencing GATA3 by siRNA led to decrease in tumor cell viability. Our data showed that silencing GATA3 increased the release of IL-4 and IL-13 from EOC cells, which leads to M2 cell polarization from M0 cells. Our results suggest that GATA3 released from macrophage exosomes contributes to tumor growth by affecting intracellular processes as well as tumor microenvironment. P.K. and A. El-A. contributed equally. Citation Format: Pinar Kanlikilicer, Amr Ahmed El-Arabey, Merve Denizli, Recep Bayraktar, Bulent Ozpolat, Gabriel Lopez-Berestein, Salama Abdu Salama, Adel Rashad Abd-Allah. M2-macrophage derived exosomes mediates tumor progression via GATA3-IL-4-IL-13 axis in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1981.