Pro-inflammatory M1 macrophage enhances metastatic potential of ovarian cancer cells through NF-κB activation.

Obesity is a serious health problem and critically related to poor prognosis in cancer, presumably through induction of chronic inflammation. The major culprit for cancer progression in obesity is presumed to be macrophages. Accumulation of macrophages in adipose tissue due to obesity induced chronic inflammation has been observed. However, obesity-induced macrophage accumulation related to ovarian cancer progression remains unclear. So, the role of macrophage in cancer progression is needed to be further defined for therapeutic intervention. Here we determined the effect of macrophage type 1 (M1 macrophage) on ovarian cancer cells in relation to the metastasis. Ovarian cancer cell lines (PA-1, SKOV3) and monocyte-derived macrophages were used in this study. Treatment with M1 macrophage conditioned media on ovarian cancer cells increased the metastatic potential, such as migration and invasion capabilities. Interestingly, upon treatment with M1 macrophage conditioned media, nuclear translocation of NF-κB, p60, and p50, from the cytosol was enhanced together with increased transcriptional activity of the NF-κB. Pre-treatment with TPCK (NF-κB inhibitor) and NF-κB siRNA on ovarian cancer cells suppressed M1 macrophage-induced metastatic potential. Furthermore, Treatment of TNF-α on ovarian cancer cells showed NF-κB activation. Co-treatment with TNF-α inhibitor, etanercept, and M1 macrophage conditioned media on ovarian cancer cell lines reversed M1 macrophage conditioned media induced NF-κB activation. Taken together, TNF-α released from M1 macrophage increased metastatic potential in ovarian cancer cells through the activation of NF-κB signaling pathway. These results provide a new insight into the critical role of M1 macrophage in the tumor microenvironment in ovarian cancer.