The significance of Gro-α in modulating omental metastasis of ovarian cancer cells

Abstract

Metastatic cancer progression is the major cause leading to the high mortality of ovarian cancer. Omental metastasis is the most common route of ovarian cancer. However, the underlying molecular mechanism of how omentum modulating ovarian cancer colonization remains unclear. Our previous studies have found that TAK1/NFkB signalling cascade is required for ovarian cancer cell aggressiveness and could be activated by omentum conditioned medium (OCM)1, suggesting that there are some factors in OCM playing activators for this pathway. In this study, we identified that growth-regulated oncogene α (Gro-α) is the main chemokine highly upregulated in OCM. Importantly, we found that Gro-α could significantly increase ovarian cancer cell migration and proliferation. In contrast, the effects of GRO-α were aborgated by the TAK1 inhibitor, 5Z-(7)-oxozeaenol. Biochemical studies demonstrated GRO-α remarkably elevated the expression levels of p-TAK1S412, p-IkBα and p-IKK. These pilot data suggest that Gro-α secreted from omentum plays as a key chemokine in activating TAK1/NFkB pathway in ovarian cancer cells. The functional effects of GRO and TAK1/NFkB signaling cascade in omental metastasis will be further investigated on primary ovarian cancer cells isolated from ovaries and omenta, as well as using ex vivo and in vivo tumorigenic models. This study will provide a model of understanding of the impact of tumor microenvironement in modulating metastatic colonization of ovarian cancer.