Omental Endothelial Cells Drive Ovarian Cancer Growth

OMENTAL endothelium has emerged as a potential driver of ovarian cancer growth, challenging the view that mature adipocytes are required to support tumour expansion within the peritoneal cavity.

Study Challenges Adipocyte Role

The omentum, a specialised adipose tissue within the peritoneum, is a primary site for ovarian cancer dissemination. Omental adipocytes have been thought to support tumour growth by supplying lipids, with previous evidence partly based on models involving global fatty acid-binding protein 4 (FABP4) deficiency.

Minz and colleagues from Washington University, USA, directly investigated whether mature adipocytes were necessary for peritoneal ovarian cancer growth. They used mice congenitally lacking mature adipocytes within the peritoneal cavity, including the omentum, and assessed several ovarian cancer models: ID8p53^−/−Brca2^−/−, BPPNM and KPCA.

Tumours Target Adipose-Associated Regions

Across the different models, tumours continued to preferentially seed adipose-associated regions despite the absence of mature adipocytes. Loss of mature adipocytes did not impair peritoneal tumour expansion.

However, removing the adipocyte-free omentum substantially reduced tumour burden. These findings indicated that features of the omental environment other than mature adipocytes may be supporting ovarian cancer growth.

The researchers then used single-cell transcriptomic analyses of murine and human tissue to investigate the cellular characteristics of the omental niche. Lipid-handling gene expression, including FABP4, was enriched in omental endothelial cells both under steady-state conditions and in tumour-bearing tissue.

Endothelial FABP4 Supports Tumour Growth

Further investigation focused on FABP4 within endothelial cells. Endothelial-specific deletion of FABP4 reduced omental tumour expansion and limited tumour vascular complexity.

Together, the findings suggested that mature adipocytes were not required for ovarian cancer growth in the omentum. Instead, the data highlighted the omental niche endothelium and its lipid-handling characteristics as potential contributors to tumour progression.

Further investigation will be needed to establish how this pathway contributes to ovarian cancer dissemination and whether targeting endothelial features of the omental niche could have therapeutic relevance.

Reference

Mintz RL et al. Peritoneal ovarian cancer growth in the omentum proceeds independently of mature adipocytes. Nat Commun. 2026;DOI: https://doi.org/10.1038/s41467-026-76471-x.

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