Abstract

BackgroundSarcoids are the mostcommon skin tumors in horses, characterized by rare regression, invasiveness and high recurrence following surgical intervention and Delta Papillomaviruses are widely recognized as the causative agents of the disease. In order to gain new insights into equine sarcoid development, we have evaluated, in 25 equine sarcoids, by immunohistochemistry and western blotting analysis, the expression levels of VEGF, Ki67 and bcl-2. Moreover, we have measured microvessel density and specific vessel parameters.ResultsAll sarcoid samples showed a strong and finely granular cytoplasmatic staining for VEGF in the majority (90%) of keratinocytes, sarcoid fibroblasts and endothelial cells. Numerous small blood vessels, immunostained with Von Willebrand factor, often appeared irregular in shape and without a distinct lumen, with mean values of microvessel area and perimeter lower than normal. Moreover, in all sarcoid samples, Ki67 immunoreactivity was moderately positive in 5–10% of dermal sarcoid fibroblasts, while Bcl2 immunoreactivity was detected in 52% of the sarcoid samples, with a weak staining in 20–50% of dermal sarcoid fibroblasts. Biochemical analysis was consistent with immunohistochemical results.ConclusionsThis study has provided evidence that in equine sarcoid: VEGF was strongly expressed; the increased number of vessels was not associated with their complete maturation, probably leading to a hypoxic condition, which could increase VEGF synthesis; the levels of sarcoid fibroblasts proliferation were very low. Concluding, VEGF may have a role in equine sarcoid development, not only through the increase of angiogenesis, but also through the control of sarcoid fibroblast activity.

Highlights

  • Sarcoids are the mostcommon skin tumors in horses, characterized by rare regression, invasiveness and high recurrence following surgical intervention and Delta Papillomaviruses are widely recognized as the causative agents of the disease

  • This study has provided evidence that in equine sarcoid: Vascular endothelial growth factor (VEGF) was strongly expressed; the increased number of vessels was not associated with their complete maturation, probably leading to a hypoxic condition, which could increase VEGF synthesis; the levels of sarcoid fibroblasts proliferation were very low

  • Concluding, VEGF may have a role in equine sarcoid development, through the increase of angiogenesis, and through the control of sarcoid fibroblast activity

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Summary

Introduction

Sarcoids are the mostcommon skin tumors in horses, characterized by rare regression, invasiveness and high recurrence following surgical intervention and Delta Papillomaviruses are widely recognized as the causative agents of the disease. VEGF, known as vascular permeability factor (VPF), is a member of the platelet-derived growth factor (PDGF) family of growth factors, having a potent angiogenic activity and an Martano et al BMC Veterinary Research (2018) 14:266 important role in the modulation of ECM homeostasis and remodeling [18, 19] It is involved in numerous physiological and pathological processes, such as embryonic development [20], bone formation [21] wound healing [22] and cancer [23,24,25,26,27], in which it is up-regulated by oncogene expression, growth factors and hypoxia [28,29,30]. It has been reported that Human Papillomavirus type 16 E6 and E7 oncoproteins may contribute to tumor angiogenesis by direct activation of the VEGF gene promoter in human lung and cervical carcinoma [31,32,33]

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