CD146+CAFs promote progression of endometrial cancer by inducing angiogenesis and vasculogenic mimicry via IL-10/JAK1/STAT3 pathway

作者：Zhicheng Yu, Qian Zhang, Sitian Wei, Yang Zhang, Ting Zhou, Qi Zhang, Rui Shi, Dmitry Aleksandrovich Zinovkin, Zahidul Islam Pranjol, Jun Zhang, Hongbo Wang · 发表于：Cell Communication and Signaling · 年份：2024 · DOI：10.1186/s12964-024-01550-9 · 被引用次数：43 · 研究领域：Angiogenesis and VEGF in Cancer、Cancer Cells and Metastasis、Endometriosis Research and Treatment

Abstract Heterogeneous cancer-associated fibroblasts (CAFs) play important roles in cancer progression. However, the specific biological functions and regulatory mechanisms involved in endometrial cancer have yet to be elucidated. We aimed to explore the potential mechanisms of heterogeneous CAFs in promoting endometrial cancer progression. The presence of melanoma cell adhesion molecule (MCAM; CD146) positive CAFs was confirmed by tissue multi-immunofluorescence (mIF), and fluorescence activated cell sorting (FACS). The biological functions were determined by wound healing assays, tuber formation assays and cord formation assays. The effects of CD146 + CAFs on endometrial cancer cells were studied in vitro and in vivo. The expression level of interleukin 10 (IL-10) was measured by quantitative real time polymerase chain reaction (qRT-PCR), western boltting and enzyme linked immunosorbent assays (ELISAs). In addition, the transcription factor STAT3 was identified by bioinformatics methods and chromatin immunoprecipitation (ChIP). A subtype of CAFs marked with CD146 was found in endometrial cancer and correlated with poor prognosis. CD146 + CAFs promoted angiogenesis and vasculogenic mimicry (VM) in vitro. A xenograft tumour model also showed that CD146 + CAFs can facilitate tumour progression. The expression of IL-10 was elevated in CD146 + CAFs. IL-10 promoted epithelial-endothelial transformation (EET) and further VM formation in endometrial cancer cells via the janus kinas...