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

Sep 21, 2026

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Heterogeneous cancer-associated fibroblasts (CAFs) drive cancer progression, yet their specific roles in endometrial cancer remain unclear. This study identifies melanoma cell adhesion molecule (MCAM/CD146) positive CAFs in endometrial cancer using multiimmunofluorescence and FACS, then evaluates function through wound healing, tuber and cord formation assays in vitro and in vivo. CD146+CAFs enhance angiogenesis and vasculogenic mimicry (VM) and correlate with poor prognosis. Mechanistically, IL-10 is elevated and activates JAK1/STAT3 signaling, promoting epithelial-endothelial transformation via IL-10/JAK1/STAT3.

LanguageEnglish

CategoryHealthcare

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Abstract

Introduction

Yu etal. Cell Communication and Signaling (2024) 22:170 [https://doi.org/10.1186/s12964-024-01550-9](https://doi.org/10.1186/s12964-024-01550-9) Cell Communication and Signaling RESEARCH Open Access CD146 + CAFs promote progression of endometrial cancer by inducing angiogenesis and vasculogenic mimicry via IL-10/JAK1/STAT3 pathway Zhicheng Yu1,2†, Qian Zhang1†, Sitian Wei1, Yang Zhang1, Ting Zhou1, Qi Zhang1, Rui Shi1, Dmitry Zinovkin3, Zahidul Islam Pranjol4, Jun Zhang1* and Hongbo Wang1,5* 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 multiimmunofluorescence (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 kinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) signalling pathway. This process could be blocked by the JAK1/STAT3 inhibitor niclosamide. Mechanically, STAT3 can bind to the promoter of cadherin5 (CDH5) to promote its transcription which may be stimulated by IL-10 . We concluded that CD146+CAFs could promote angiogenesis and VM formation via the IL-10/JAK1/STAT3 signalling pathway. These findings may lead to the identification of potential targets for antiangiogenic therapeutic strategies for endometrial cancers. Keywords Endometrial cancer, Cancer-associated fibroblast, Interleukin 10, Vasculogenic mimicry †Zhicheng Yu and Qian Zhang contributed equally to this work. *Correspondence: Jun Zhang [2418009102@qq.com](2418009102@qq.com)[ ](2418009102@qq.com)Hongbo Wang[hb_wang1969@sina.com](hb_wang1969@sina.com) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creativecommons.org/licenses

FAQs

What role do CD146-positive cancer-associated fibroblasts play in endometrial cancer?

CD146+CAFs promote angiogenesis and vasculogenic mimicry, facilitating endometrial cancer progression in vitro and in vivo.

How was the CD146+ CAF subtype identified and its function tested?

CD146+ CAFs were confirmed by tissue multiimmunofluorescence and quantified by FACS, then assessed using wound healing, tuber formation, and cord formation assays.

Which signaling pathway links IL-10 to VM formation in endometrial cancer cells?

IL-10 activates the JAK1/STAT3 pathway, promoting epithelial-endothelial transformation and further VM formation; this effect can be blocked by the JAK1/STAT3 inhibitor niclosamide.

Sep 21, 2026

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