Ovarian cancer metastasis to the human omentum disrupts organ homeostasis and induces fundamental tissue reprogramming

The omentum, a visceral adipose tissue critical for metabolic, immunological, and stem cell functions, is a key site for ovarian cancer metastasis. However, its role in homeostasis and response to metastasis is not fully understood. Using single-cell transcriptomics, we profiled different omental regions in patients with benign conditions and ovarian cancer metastasis. We found that the benign omentum maintains stable cell composition and a stem cell niche. Metastasis led to immune landscape diversification and loss of mesothelial and progenitor cells. The lesser omentum, often spared in surgery, emerged as a premetastatic niche with neutrophil infiltration, NETosis, and micrometastases. Cancer cells orchestrated reprogramming of resident cells, inducing regulatory, anti-adipogenic, and immunosuppressive phenotypes across the omentum. This cell atlas illuminates the cellular and molecular determinants of organ homeostasis and reveals a high degree of plasticity and cellular reprogramming promoted by cancer colonization.