Omental support of ovarian tumor cell growth is unabated in the absence of mature adipocytes

The omentum, a specialized adipose tissue arising off the stomach, is a key premetastatic niche for ovarian cancer metastasis and growth within the peritoneum. Why the omentum promotes optimal ovarian cancer growth remains unclear, but the prevailing concept is that omental adipocytes and the accompanying metabolic exchange of FABP4-binding fatty acids are critical. Here, we generated mice lacking mature adipocytes in all peritoneum tissues, including the omentum. ID8p53–/–Brca2–/– tumors retained a propensity to seed at regions typically associated with adipose depots, even without mature adipocytes. However, the lack of mature adipocytes did not suppress tumor expansion in the peritoneum, whereas removing the adipocyte-free omentum did. Single-cell RNA sequencing analysis revealed that endothelial FABP4 was especially high in the omentum, potentially accounting for the role of FABP4 in tumor growth rather than adipocyte FABP4, as previously thought. Thus, whether and how tumor cell-adjacent adipocytes impact tumor progression needs re-evaluation