Matrix metalloproteinase-9 associated with heparan sulphate chains of GPI-anchored cell surface proteoglycans mediates motility of murine colon adenocarcinoma cells.
Using murine colon adenocarcinoma-derived clones with different metastatic potentials, the cellular localization of matrix metalloporteinase-9 (MMP-9) and its role in the cell motility were examined. Highly metastatic LuM1 clone aggressively invaded into adjacent tissue in vivo, but low metastatic NM11 clone did not. As compared with the NM11 clone, the LuM1 clone expressed and secreted a remarkably large amount of MMP-9, and exhibited higher abilities of cell migration and invasion in vitro, which were suppressed by MMP-2/MMP-9 inhibitor IV. MMP-9, exhibiting high affinity to heparin, was demonstrated to be condensed on tips of cellular podia. Treatment of the cells with heparitinase-I or heparin resulted in release of MMP-9 from the cell surface, which caused concomitant suppression of their motility to a similar level to that with the MMP inhibitor. Immunoprecipitation of a LuM1 cell lysate with an anti-MMP-9 antibody resulted in co-precipitation of phosphatidylinositol-specific phospholipase C-susceptible heparan sulphate proteoglycans having 66 and 64 kDa core proteins. Taken together, the present results demonstrate that secreted MMP-9 associates with glypican-like proteoglycans through their heparan sulphate chains, and plays a crucial role in cell motility of LuM1 cells.
Koyama
Yoshie
Y
Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Kamigamo Motoyama, Kitaku, Kyoto 603-8555, Japan.
Naruo
Hideaki
H
Yoshitomi
Yasuo
Y
Munesue
Seiichi
S
Kiyono
Shinsuke
S
Kusano
Yuri
Y
Hashimoto
Katsunori
K
Yokoi
Toyoharu
T
Nakanishi
Hayao
H
Shimizu
Satoru
S
Okayama
Minoru
M
Oguri
Kayoko
K
D000230:Adenocarcinoma / Q000201:enzymology / Q000556:secondary; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology*; D002465:Cell Movement; D002999:Clone Cells; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D017261:Glycosylphosphatidylinositols; D019812:Heparan Sulfate Proteoglycans; D008565:Membrane Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D020780:Matrix Metalloproteinase 9