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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2015 ; 290
(22
): 13763-78
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English Wikipedia
Recruitment of Matrix Metalloproteinase-9 (MMP-9) to the Fibroblast Cell Surface
by Lysyl Hydroxylase 3 (LH3) Triggers Transforming Growth Factor-? (TGF-?)
Activation and Fibroblast Differentiation
#MMPMID25825495
Dayer C
; Stamenkovic I
J Biol Chem
2015[May]; 290
(22
): 13763-78
PMID25825495
show ga
Solid tumor growth triggers a wound healing response. Similar to wound healing,
fibroblasts in the tumor stroma differentiate into myofibroblasts (also referred
to as cancer-associated fibroblasts) primarily, but not exclusively, in response
to transforming growth factor-? (TGF-?). Myofibroblasts in turn enhance tumor
progression by remodeling the stroma. Among proteases implicated in stroma
remodeling, matrix metalloproteinases (MMPs), including MMP-9, play a prominent
role. Recent evidence indicates that MMP-9 recruitment to the tumor cell surface
enhances tumor growth and invasion. In the present work, we addressed the
potential relevance of MMP-9 recruitment to and activity at the surface of
fibroblasts. We show that recruitment of MMP-9 to the fibroblast cell surface
occurs through its fibronectin-like (FN) domain and that the molecule responsible
for the recruitment is lysyl hydroxylase 3 (LH3). Functional assays suggest that
both pro- and active MMP-9 trigger ?-smooth muscle actin expression in cultured
fibroblasts, reflecting myofibroblast differentiation, possibly as a result of
TGF-? activation. Moreover, the recombinant FN domain inhibited both
MMP-9-induced TGF-? activation and ?-smooth muscle actin expression by displacing
MMP-9 from the fibroblast cell surface. Together our results uncover LH3 as a new
docking receptor of MMP-9 on the fibroblast cell surface and demonstrate that the
MMP-9 FN domain is essential for the interaction. They also show that the
recombinant FN domain inhibits MMP-9-induced TGF-? activation and fibroblast
differentiation, providing a potentially attractive therapeutic reagent toward
attenuating tumor progression where MMP-9 activity is strongly implicated.