The importance of tumor microenvironment in cancer progression has been recognized recently. However, factors associated with the tumor microenvironment are diverse and the molecular mechanisms are needed to be further defined for therapeutic intervention. Here we focused on the interaction between obesity related inflammatory cell, macrophage type 1 (MФ-1), and ovarian cancer cells in relation to metastasis. Two types of ovarian cancer cell lines; PA-1 and SKOV3, and monocyte-derived macrophages were used in this study. In the treatment with MФ-1 conditioned media, only SKOV3 cells were affected in proliferation activity. However migration and invasion were promoted by treatment with MФ-1 conditioned media in both ovarian cancer cells. In parallel, MФ-1 conditioned media treatment increased TWIST, EMT related gene. Interestingly, TWIST expression was correlated with protein expression levels of nuclear NF-κB (p65 and p50). Upon MФ-1 conditioned media treatment, nuclear translocation level and transcriptional activity of the NF-κB increased. Also, TPCK, NF-κB inhibitor suppressed invasion activity by MФ-1 conditioned media, in parallel with down-regulation of TWIST expression. Taken together, MФ-1 promoted EMT related metastatic potential in ovarian cancer cells through NF-κB signaling pathway. These results provide a new insight into the obesity related tumor microenvironment in ovarian cancer cell progression.

Citation Format: Un-Tek Jo, YongSang Song. M1 macrophages promote ovarian cancer metastasis through NF-κB/TWIST axis signaling pathway. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3241.