CD146+CAFs promote progression of endometrial cancer by inducing angiogenesis and vasculogenic mimicry via IL-10/JAK1/STAT3 pathway
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View abstract on PubMed
Summary
This summary is machine-generated.Cancer-associated fibroblasts expressing CD146 promote endometrial cancer progression by enhancing angiogenesis and vasculogenic mimicry. This occurs through the IL-10/JAK1/STAT3 pathway, offering potential therapeutic targets.
Area Of Science
- Oncology
- Cell Biology
- Cancer Research
Background
- Heterogeneous cancer-associated fibroblasts (CAFs) are crucial in cancer progression, but their specific roles in endometrial cancer remain unclear.
- Understanding CAFs' regulatory mechanisms is vital for developing targeted therapies.
Purpose Of The Study
- To investigate the mechanisms by which heterogeneous CAFs, specifically CD146-positive CAFs (CD146+CAFs), promote endometrial cancer progression.
- To elucidate the role of Interleukin-10 (IL-10) and the JAK1/STAT3 signaling pathway in CD146+CAF-mediated tumor growth.
Main Methods
- Confirmed CD146+CAFs using multi-immunofluorescence (mIF) and fluorescence-activated cell sorting (FACS).
- Assessed CAF functions via wound healing, tube formation, and cord formation assays.
- Investigated CD146+CAF effects in vitro and in vivo xenograft models.
- Measured IL-10 expression using qRT-PCR, Western blotting, and ELISAs.
- Identified STAT3 involvement through bioinformatics and chromatin immunoprecipitation (ChIP).
Main Results
- CD146+CAFs were identified in endometrial cancer and associated with poor prognosis.
- CD146+CAFs significantly promoted angiogenesis and vasculogenic mimicry (VM) in vitro and facilitated tumor growth in vivo.
- Elevated IL-10 expression in CD146+CAFs was observed.
- IL-10 promoted epithelial-endothelial transformation (EET) and VM via the JAK1/STAT3 pathway, which was inhibited by niclosamide.
- STAT3 was found to bind the CDH5 promoter, potentially stimulated by IL-10.
Conclusions
- CD146+CAFs promote endometrial cancer angiogenesis and VM through the IL-10/JAK1/STAT3 signaling pathway.
- This pathway involves STAT3 binding to the CDH5 promoter.
- These findings highlight CD146+CAFs and the IL-10/JAK1/STAT3 pathway as potential therapeutic targets for anti-angiogenic strategies in endometrial cancer.
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