The inflammatory cytokine TNF-α is an important tumor promoter in a variety of experimental animal models whether produced by initiated epithelial cells or by stromal components. This cytokine is also produced by the malignant cells of advanced cancers, its presence often being associated with poor prognostic factors. Epithelial ovarian cancer is one cancer in which tumor cell TNF-α production has been described. In tissue culture, malignant ovarian epithelial cells secrete picogram quantities of TNF-α protein. In human ovarian cancer biopsies, epithelial TNF-α is associated with increased tumor grade and expression of the chemokine receptor CXCR4. Treatment of ovarian cancer cells with exogenous TNF-α in vitro enhances production of a range of other inflammatory cytokines and expression of CXCR4 and in a tumor xenograft model, TNF-α treatment converted ascitic ovarian xenograft tumors to peritoneal masses with well-developed stroma. Furthermore, inhibition of endogenous TNF-α protein, by RNA interference (RNAi) technology or neutralizing antibody, reduced expression of the chemokine receptor CXCR4 and the cytokine interleukin-6 in ovarian cancer cells.
Kulbe H, Thompson R, Wilson JL, et al. The Inflammatory Cytokine Tumor Necrosis Factor-α Generates an Autocrine Tumor-Promoting Network in Epithelial Ovarian Cancer Cells. Cancer research. 2007;67(2):585-592.