Figure 8

Schematic proposal of EGF- or TNF-responsive chemokines in ovarian cancer cells. EGFR, frequently overexpressed in high-grade ovarian cancer, activates Akt and Erk in response to EGF, resulting to secretion of proinflammatory chemokines such as CCL20, CXCL1-3, and CXCL8, all of which contain κB sites in their promoters. Also TNF, a proinflammatory cytokine abundantly expressed in ovarian cancer, induces NF-κB activation followed by secretion of proinflammatory chemokines. Although the response to TNF or EGF is cell-type specific, ovarian cancer cells mainly induce proinflammatory chemokines such as CCL20, CXCL1-3, and CXCL8 through additive or synergistic interaction between EGF and TNF. The enhanced chemokines reinforce the proinflammatory tumor microenvironment for ovarian cancer progression such as peritoneal tumor dissemination and the production of massive ascites which promote the higher mortality rates seen with this malignancy.