Publication: Activation of matrix metalloproteinase (MMP)-2 by membrane type 1-MMP and abnormal immunolocalization of the basement
membrane components laminin and type IV
collagen in canine spontaneous hemangiosarcomas
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Date
2009
Authors
Murakami, M. ; Sakai, Hidetaka ; Kodama, A. ; Mori, T. ; Yanai, T. ; Maruo, K. ; Masegi, T.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
We performed immunohistochemical
investigation of the basement membrane (BM)
components, namely, type IV collagen and laminin, in
83 canine hemangiosarcomas (HSAs), 22 hemangiomas,
and some granulation tissues (GTs). Additionally, we
analyzed the expression and activities of matrix
metalloproteinase (MMP)-2, MMP-9, and membrane
type 1-MMP (MT1-MMP) using the same samples by
immunohistochemistry and gelatin zymography to
investigate whether MMPs were associated with the BM
degradation. In immunohistochemistry for the BM
components, many HSAs showed discontinuous
linear/negative immunoreactivity in the BM (type IV
collagen: 49.4%/14.5%, laminin: 60.3%/10.8%,
respectively). In contrast, almost all hemangiomas
showed continuous staining in the BM (type IV
collagen: 90.9%, laminin: 95.5%, respectively).
Interestingly, positive cytoplasmic immunoreactivity for
type IV collagen and laminin was observed in 97.6% and
91.6% HSA, respectively. Although MMP-9
immunoreactivity wasn’t detected in neoplastic and
active angiogenic endothelial cells (ECs), MMP-2 was
detected in all ECs of GTs and in neoplastic cells of both
vascular tumors. A strong immunoreactivity for MT1-
MMP was observed in active angiogenic ECs in GTs and
in neoplastic ECs in HSAs. However, almost all
hemangiomas showed weak/negative immunoreactivity.
In gelatin zymography, significantly strong activity of
active MMP-2 was observed in HSAs, similar to that in active angiogenesis in GTs; however, weak/no activity of
active MMP-2 was detected in hemangiomas. In canine
HSA, neoplastic cells had active MMP-2, possibly
activated by MT1-MMP, and discontinuous status of BM
might be associated with activity of active MMP-2.
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