Detection of vasculogenic mimicry in equine ocular, oronasal, and genital squamous cell carcinoma.
Authors: Schwarz Sophie, Kummer Stefan, Klang Andrea, Walter Ingrid, Nell Barbara, Brandt Sabine
Journal: PloS one
Summary
# Editorial Summary: Vasculogenic Mimicry in Equine Squamous Cell Carcinoma Squamous cell carcinoma remains the most common malignancy in horses, yet its mechanisms of progression and spread are incompletely understood. Schwarz and colleagues investigated whether equine SCCs employ vasculogenic mimicry—a process in which tumour cells themselves form blood vessel-like structures independent of endothelial cells—across 43 naturally occurring lesions from ocular, oronasal, and genital sites. Using a rigorous multi-stage approach combining PCR screening for equine papillomavirus, Periodic Acid-Schiff and immunohistochemical staining, and triple immunofluorescence analysis, the team identified vasculogenic mimicry in 13 tumours (31% of the cohort), distributed across all three anatomical regions: six genital, three oronasal, and four ocular SCCs. Notably, the mimicry channels were lined by cancer cells rather than endothelial cells yet contained functional erythrocytes and recruited pericyte support cells, suggesting tumours actively engineer these pseudo-vessels to enhance their blood supply and invasive capacity. This represents the first documented evidence of vasculogenic mimicry in equine malignancies and has significant implications for understanding why equine SCCs are notoriously difficult to treat—tumours capable of forming their own vascular networks may evade conventional anti-angiogenic strategies and progress more aggressively, particularly in genital and oronasal lesions where papillomavirus association is prevalent.
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Practical Takeaways
- •SCC tumors in horses employ a sophisticated survival mechanism (vasculogenic mimicry) that may explain why they are difficult to treat; understanding this biology may inform future therapeutic strategies
- •Genital and oronasal SCCs show strong association with equine papillomavirus type 2, suggesting potential targets for prevention or adjunctive treatment that differ from ocular SCCs
- •The presence of pericyte recruitment around pseudo-vessels indicates tumor cells are actively promoting vascularization, reinforcing the importance of early detection and aggressive intervention before these adaptive mechanisms establish
Key Findings
- •13 of 43 equine SCC lesions (30%) demonstrated vasculogenic mimicry with CD31-negative, PAS-positive vessel-like structures containing erythrocytes
- •All genital and 50% of oronasal tumors tested positive for equine papillomavirus type 2, while ocular tumors were EcPV-negative
- •Tumor cells forming vasculogenic mimicry channels recruited pericytes (Col4 and α-SMA positive) to enhance channel formation and stability
- •This is the first documented evidence of vasculogenic mimicry in equine cancer and animal squamous cell carcinoma