Endosialin promotes vascular maturation by inhibiting Cyr61 expression in melanoma metastasis

Lijun Yang^1,2*Tong Lu²Hongtao Song²Chao Xu²Shaojie Liu²Zhite Zhao²Lunbiao Gan²Fa Yang²Zhihao Hu²Weihong Wen²Donghui Han²Weijun Qin²

• ¹Department of Urology, Xijing Hospital, Air Force Medical University., Xi'an, China
• ²Air Force Medical University, Xi'an, Shaanxi Province, China

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.