ORIGINAL RESEARCH article
Front. Oncol.
Sec. Skin Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1528288
Endosialin promotes vascular maturation by inhibiting Cyr61 expression in melanoma metastasis
Provisionally accepted- 1Department of Urology, Xijing Hospital, Air Force Medical University., Xi'an, China
- 2Air Force Medical University, Xi'an, Shaanxi Province, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Extensive tumor cell metastasis is associated with poor patient prognosis.Tumor endothelial cells demonstrate distinct proangiogenic phenotypes compared to normal endothelial cells, partially mediated by pericyte-derived secreted factors.Endosialin, a pericyte biomarker implicated in vascular maturation and metastatic progression, remains mechanistically undefined in this context.Methods: B16F10 melanoma cells were injected via caudal vein into Endosialin knockout (EN KO ) and wildtype mice. Lung metastases were quantified through hematoxylin-eosin (HE) staining. Vascular architecture was analyzed using Evans blue perfusion and CD31 immunofluorescence. Molecular mechanisms were investigated through western blotting, qPCR, proliferation assays, and in vitro lumen formation models.Results: Bioinformatics analysis revealed Endosialin overexpression correlates with enhanced angiogenesis and poor clinical outcomes. Endosialin deficiency significantly reduced pulmonary metastasis burden. Vascular profiling showed EN KO mice exhibited increased small-diameter vessels (<50 μm) and reduced mature vessels (≥50 μm).Mechanistically, Endosialin regulates vascular maturation through Erk1/2-mediated suppression of Cyr61 in pericytes Conclusion: Endosialin facilitates melanoma metastasis by promoting vascular maturation via Erk1/2-Cyr61 signaling axis in pericytes.
Keywords: Endosialin/CD248/TEM-1, Cyr61/CCN1, Melanoma, Angiogenesis, Tumor metastasis
Received: 14 Nov 2024; Accepted: 08 Jul 2025.
Copyright: © 2025 Yang, Lu, Song, Xu, Liu, Zhao, Gan, Yang, Hu, Wen, Han and Qin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lijun Yang, Department of Urology, Xijing Hospital, Air Force Medical University., Xi'an, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.