Development of ovarian cancer, the most lethal malignancy in women, involves genetic changes within epithelial cells as well as alteration in their neighboring stromal microenvironment. Secreted factors from the inflammatory network are known to directly promote the stromal microenvironment to become tumor-prone, although the detailed mechanisms remain to be elucidated. Our preliminary data showed that ovarian cancer epithelial cells secrete IL-1β that functionally represses the expression of tumor suppressor p53 protein in normal ovarian fibroblasts. Suppression of p53 in ovarian stromal fibroblasts promotes secretion of inflammatory cytokines in an NF-κB-dependent manner. Significantly, ovarian fibroblasts with attenuated p53 promote the initiation and growth of ovarian cancer in a mouse xenograft model in vivo. Thus, our preliminary data strongly suggest that IL-1β-mediated p53-attenuation, which works in synergy with NF-κB to induce trans-differentiation toward a pro-secretory, pro-stimulatory paracrine CAFs phenotype to facilitate the ovarian cancer growth in vivo.