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Figure 2.5 Human meprin a is a pro-angiogenic enzyme. A Morpholino knockdown
of meprin a in zebrafish embryos revealed dramatic defects in the vascular
system (A,B). 41 Microangiography (with TRITC-Dextran) exhibited a
drastically reduced vascular system without any intersegmental blood
vessels (B) in meprin a morphants, compared to the non-injected wild type
(WT) zebrafish (A). Additionally, erythrocytes accumulated in the ventral
caudal tail region (C), possibly as a consequence of this sprouting failure.
CA: caudal artery; CV: caudal vein; DA: dorsal aorta; DLAV: dorsal
longitudinal anastomotic vessel; H: heart; ISV: intersegmental vessels; L:
liver; PCV: posterior cardinal vein; PCeV: posterior cerebral vein (scale
bar: 250 mm).
Meprin metalloproteases are expressed in several different tumors, e.g. breast
and colon carcinoma. 80,81 In cultured colon carcinoma cells, meprin a is secreted
not only apically but also basolaterally. Hence, the proteolytic potential of
meprins is directed towards the extracellular matrix, thereby possibly affecting
proliferation and migration of tumour cells into the surrounding tissue. This is
supported by cell-culture experiments with actinonin-treated human breast
carcinoma cells, which resulted in decreased invasiveness in vitro. 81
However, the pro-angiogenic effect of meprin a might be even more
important for cancer pathology, particularly regarding the expression of the
protease in relation to tumor progression. 88 Sabo and co-workers showed that
meprin a mRNA expression is significantly decreased in high-grade dysplasia. 82
In another study, Fox and colleagues demonstrated that meprin a is down-
regulated in esophageal adenocarcinoma, suggesting that this protease may be
involved in processes other than extracellular matrix degradation during Bar-
rett's esophagus-associated neoplastic progression. 83 Recently, it was demon-
strated that both meprins are capable of processing procollagen III, thereby
enhancing fibril assembly, a role which could be contrary to metastasis. 48
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