Abstract
Background: equine sarcoids are the most frequent skin tumors in equidae worldwide. It is well known that delta bovine papillomaviruses are their causative agents. We have recently shown the presence in equine sarcoids of abnormal vessel structures, which could cause a hypoxic condition. The aim of this study was to analyze the expression of hypoxia-inducible factor-1 alpha (HIF-1α) in a subset of BPV positive equine sarcoids and explore the relationship with vascular endothelial growth factor (VEGF) expression. Results: 80% of equine sarcoids showed strong cytoplasmic staining in >60% of neoplastic fibroblasts, while 20% of samples showed a moderate cytoplasmic staining in 40–60% of neoplastic fibroblasts for HIF-1α. Results of Western blotting (WB) were consistent with immunohistochemistry (IHC). Moreover, a positive correlation between HIF-1α and VEGF expression (r = 0.60, p < 0.01) was observed. Conclusion: we have shown that HIF-1α was strongly expressed in equine sarcoid. The upregulation of HIF-1α has been described in numerous tumors and can be modulated by many proteins encoded by transforming viruses. Thus, it is also possible that BPV could have a relevant role in HIF-1α pathway regulation, contributing to the development of equine sarcoids by promoting HIF-1α/VEGF mediated tumor angiogenesis.
Highlights
Equine sarcoids are the most frequent fibroblastic benign skin tumor in equidae worldwide, with prevalence rates of 0.5–2.0% [1,2]
We have recently shown an overexpression of vascular endothelial growth factor (VEGF) and abnormal vessel structures [27] in equine sarcoids, which could cause a hypoxic condition, leading to an upregulation of HIF-1α
As VEGF [27,29,32,34,60], HIF-1α is overexpressed in a large variety of tumors [60,63], and its association with unfavorable prognosis has been reported, as it activates genes that play a relevant role in angiogenesis, invasion, and metastasis [57,59,64]
Summary
Equine sarcoids are the most frequent fibroblastic benign skin tumor in equidae worldwide, with prevalence rates of 0.5–2.0% [1,2]. They often form from scar tissue or sites of a previous wound or trauma, on the head, the limbs, the ventrum, and the paragenital region [3]. Equine sarcoids have a multifactorial cause [9]; it has been proved that there is a strong correlation between permanent infection with delta bovine papillomaviruses (BPV type 1, 2 and 13), and persistent and progressive sarcoids [7,10,11].
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