Abstract:
Introduction: Bovine papillomaviruses −1/−2 (BPVs) are small non-enveloped
double-stranded DNA viruses able to infect the skin of bovids and equids,
causing development of neoplastic lesions such as bovine cutaneous
fibropapillomas and equine sarcoid. Matrix metalloproteinases (MMPs) are a
group of zinc-dependent endopeptidases that degrade basal membrane and
extracellularmatrix, whose function is essential in physiological processes such
as tissue remodeling and wound healing. MMPs activity is finely regulated by
a balancing with expression of tissue inhibitors of MMPs (TIMPs), a process
that is impaired during tumour development. BPV infection is associated with
upregulation of MMPs and /or their unbalancing with TIMPs, contributing to
local invasion and impairment of extracellular matrix remodeling in equine
sarcoid; however, studies regarding this topic in bovine fibropapillomas
are lacking.
Methods: The aim of this study was to perform an immunohistochemical and
biochemical analysis on a panel of MMPs and TIMPs in BPV-2 positive bovine
cutaneous fibropapillomas vs. normal skin samples.
Results: Immunohistochemistry revealed a cytoplasmic expression of MMP-
2 (15/19), a cytoplasmic and perinuclear immunoreactivity of MMP-7 (19/19)
and MMP-9 (19/19), along with a cytoplasmic and nuclear pattern of
MMP-14 (16/19), accompanied by a cytoplasmic expression of TIMP-1
(14/19) and TIMP-2 (18/19) in tumour samples; western blotting revealed an
overexpression ofMMP-2 (8/9),MMP-7 (9/9) andMMP-9 (9/9), and a decreased
level of MMP-14 (9/9), TIMP-1 (9/9) and TIMP-2 (9/9) in tumour versus normal
skin samples. Moreover, gelatine zymography confirmed the expression of
pro-active MMP-2 (9/9) and MMP-9 (9/9) and, most importantly, indicated
the presence and increased activity of their active forms (82 and 62 kDa,
respectively) in tumour samples.
Frontiers in Veterinary Science 01 frontiersin.org
Daraban Bocaneti et al. 10.3389/fvets.2022.1063580
Discussion: This is the first study describing MMPs and TIMPs in bovine
cutaneous fibropapillomas and our results suggest that their unbalanced
expression in presence of BPV-2 may play a significant role in tumour
development. A further analysis of supplementaryMMPs and TIMPs could bring
new important insights into the papillomavirus induced tumours.
