Increased Dietary Fat Promotes Histological and Molecular Changes in Stromal Cells of Human Endometrial Cancer Xenografts
Year: 2026
Type: article
Abstract: Obesity is associated with increased risk and poorer outcomes in endometrial cancer. Dietary fat intake can influence metabolic and hormonal pathways that contribute to this risk but the specific effects on tumor-associated stromal cells remains unclear and poorly understood. We investigated transcriptomic changes induced by high fat diet (HFD; 35% fat, 60% kcal fat) in tumor cells and tumor-associated stromal cells within human endometrial cancer (EC) patient derived xenografts (PDX) established in female immunocompromised mice. Spatial transcriptomics showed HFD exposure, which may reflect the combined effects of high dietary fat, obesity, or obesity associated metabolic alterations, produced distinct gene expression profiles in tumor and stromal cells. Stromal regions from HFD mice contained adipocyte-like cells that appeared to be lipid rich along with increased expression of pathways related to adipogenesis, estrogen response, PI3K/AKT/MTOR signaling and MTORC1 signaling. In contrast stromal regions from conventional diet (CD) mice (CD; 6�t, 16%kcal fat) showed enrichment od transcripts associated with tumor suppression. Tumor cells from HFD fed mic also displayed altered expression in similar pathways but with distinct transcript differences. These findings demonstrate cell specific transcriptomic responses to HFD exposure, obesity, or related metabolic changes and highlight the active role of stromal cells in the tumor in the microenvironment. Consideration of stromal responses is critical when evaluating the influence of diet and metabolic state on EC progression and may inform strategies to mitigate obesity associated tumor risk.
Source: Figshare
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7165390513