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

ABSTRACT: The omentum, a visceral adipose tissue with critical metabolic, immunological, and stem cell functions is the preferred site for ovarian cancer metastasis. However, its role in maintaining homeostasis and its responses to metastatic colonization remain incompletely understood. Using single-cell transcriptomics, we profiled different anatomical regions of the omentum in patients with benign conditions and ovarian cancer metastasis. We cataloged the benign omentum and found stable cell type composition and preservation of a stem and progenitor niche. Upon metastatic colonization, the immune landscape diversified accompanied by a gradual loss of mesothelial and progenitor cells. The lesser omentum, which is not routinely removed during surgical debulking, was identified as a premetastatic niche characterized by neutrophil infiltration, NETosis, and the presence of micrometastases. At established metastatic sites, resident cells exhibited cancer-associated phenotypes with regulatory, anti-adipogenic, and immunosuppressive functions. Cancer cells orchestrated the cell reprogramming via a repertoire of signaling factors affecting both proximal and distal omental tissue. 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.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Sandra Goetze

PROVIDER: MSV000096327 | MassIVE | Thu Nov 07 06:36:00 GMT 2024

REPOSITORIES: MassIVE

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

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