Dataset Information

Adipocytes are dispensable in shaping the ovarian cancer tumor microenvironment in the omentum

ABSTRACT: The omentum, a specialized adipose tissue within the peritoneum, is a key metastatic niche for ovarian cancer (OC) dissemination during peritoneal carcinomatosis. The prevailing view is that omental adipocytes promote tumor growth by providinglipids, since global FABP4 deficiency curbs tumor growth. Here, we generated mice lacking mature adipocytes in the peritoneum and omentum. ID8p53–/–Brca2–/– , BPPNM, and KPCA OC cells retained a propensity to seed at regions typically associated with adipocytes, even without mature adipocytes. However, lack of mature adipocytes did not suppress peritoneal OC expansion, whereas removing the adipocyte-free omentum did. Murine and human single-cell RNA sequencing analysis revealed that endothelial FABP4 was high in the omentum. Indeed, endothelial cell-selective deficiency of FABP4 reduced OC growth in the peritoneum. These findings prompt a re-evaluation of adipocyte contributions to OC progression and point to a key role of the omental vasculature in supporting OC growth metabolically.

ORGANISM(S): Homo sapiens

PROVIDER: GSE300038 | GEO | 2026/06/15

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other
	GSE300038_RAW.tar	Raw
	filelist.txt	Txt

Items per page:

1 - 3 of 3

Similar Datasets

Project description:Background: The preferred site of metastasis in ovarian cancer (OC) is the fat-rich omentum. The interaction between cancer cells and adipocytes induces transcriptomic changes driving an invasive and pro-metastatic phenotype. Here we studied the effects of the OC cell-adipocyte crosstalk by using direct co-culture with immortalized human visceral pre-adipocytes and OC cells. Methods: OVCAR5 or OVCAR8 OC cells expressing either GFP or RFP were co-cultured with matured immortalized visceral pre-adipocyte (VNPAD). After direct co-culture, OC cells were FACS-sorted and cell proliferation, invasiveness, resistance to cisplatin were assessed. RNA-sequencing determined transcriptomic changes induced by co-culture. Immunohistochemistry (IHC) and ELISA measured C3 expression in metastatic tumors and in malignant ascites. Results: Direct co-culture with VNPAD led to increased proliferation, invasiveness and resistance to cisplatin of OC cells compared to monoculture. RNA-sequencing revealed 205 differentially expressed genes (DEGs) common to both VNPAD co-cultured OVCAR5 and OVCAR8 cells and enriched pathways such as PI3K/AKT and complement activation. Co-culture induced lipid transfer into OC cells promoted upregulation of complement C3 and C5 units, as measured at mRNA and protein levels. C3 or C5 inhibition reverted the invasive phenotype of OC cells and C3 knockdown reduced tumor progression in a xenograft model. Increased C3 expression was detected in metastatic vs. primary ovarian tumors (p<0.0001) and increased C3 secretion was observed in ascites from women with BMI > 25 (p = 0.01). C3 upregulation in OC cells was driven through activation of stress response pathway regulated by ATF4. Conclusions: Co-culture of adipocytes and cancer cells drives an invasive and chemo-resistant phenotype. These changes are induced by transfer of lipids from adipocytes to cancer cells causing activation of the complement proteins C3, C5, and of the integrated stress response pathway.

Dataset Information

Adipocytes are dispensable in shaping the ovarian cancer tumor microenvironment in the omentum

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets