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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
Lijun  YangLijun Yang1,2*Tong  LuTong Lu2Hongtao  SongHongtao Song2Chao  XuChao Xu2Shaojie  LiuShaojie Liu2Zhite  ZhaoZhite Zhao2Lunbiao  GanLunbiao Gan2Fa  YangFa Yang2Zhihao  HuZhihao Hu2Weihong  WenWeihong Wen2Donghui  HanDonghui Han2Weijun  QinWeijun Qin2
  • 1Department of Urology, Xijing Hospital, Air Force Medical University., Xi'an, China
  • 2Air Force Medical University, Xi'an, Shaanxi Province, China

The final, formatted version of the article will be published soon.

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

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