National Cancer Institute 5R37CA261952-05

Role of the pro-inflammatory omental microenvironment in ovarian cancer progression

This award supports research on the role of omentin in modulating the pro-inflammatory omental microenvironment to prevent ovarian cancer progression and metastasis, aiming to develop omentin as a therapeutic agent.

Description

High-grade serous ovarian cancer (HGSC) metastasizes preferentially to the omentum, which is a well-vascularized fold of peritoneal tissue covered by mesothelial cells and a major site of intra-abdominal fat accumulation. It was reported that HGSC and stromal cell-derived pro-inflammatory cytokines downregulate omentin (ITLN1), a novel mesothelial cell-derived adipokine to promote the invasive potential and proliferation of cancer cells in the omental microenvironment. Omentin has been shown to suppress ovarian cancer invasive potential and cell growth through suppressing MMP1 expression and cell traction force in cancer cells, and inducing a local rapid metabolic coupling between ovarian cancer cells and neighboring adipocytes. Higher pre-operative serum omentin levels in patients with HGSC are associated with longer survival times. Mice treated with omentin showed increased activated CD8+ T cell density. The study hypothesizes that omentin normalizes the pro-inflammatory omental microenvironment via upregulating anti-inflammatory TSG-6 in adipocytes, which binds to pro-inflammatory cytokines, attenuating the immunosuppressive tumor microenvironment, preventing omental metastasis, and suppressing tumor progression.

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