Peritoneal ovarian cancer growth in the omentum proceeds independently of mature adipocytes

Abstract The omentum, a specialized adipose tissue within the peritoneum, is a primary niche of ovarian cancer dissemination. Omental adipocytes are widely thought to promote tumor growth by supplying lipids, supported in part by studies using global FABP4 deficiency. Here, we directly test whether mature adipocytes are required for peritoneal ovarian cancer growth using mice congenitally lacking mature adipocytes within the peritoneal cavity, including the omentum. Across several ovarian cancer models (ID8p53 −/− Brca2 −/− , BPPNM, and KPCA), tumors preferentially seed adipose-associated regions despite the absence of mature adipocytes. Loss of mature adipocytes does not impair peritoneal tumor expansion, whereas removal of the adipocyte-free omentum significantly reduces tumor burden. Murine and human single-cell transcriptomic analyses reveal enrichment of lipid-handling gene expression, including FABP4, in omental endothelial cells at steady state and in tumor-bearing tissue. Endothelial-specific deletion of FABP4 reduces omental tumor expansion and limits tumor vascular complexity. These findings indicate that mature adipocytes are not required for omental ovarian cancer growth and highlight tumor-growth-favoring features of the omental niche endothelium.