Localization of membrane-type 1 matrix metalloproteinase in caveolae membrane domains.
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane-associated MMP that has been recently reported to have a central role in tumour cell invasion. Here we report that both the native and overexpressed recombinant forms of MT1-MMP are highly enriched in low-density Triton X-100-insoluble membrane domains that contain the caveolar marker protein caveolin 1. Moreover, the MT1-MMP-dependent activation of proMMP-2 induced by concanavalin A and cytochalasin D was correlated with the processing of MT1-MMP to its proteolytically inactive 43 kDa fragment in U-87 glioblastoma and HT-1080 fibrosarcoma tumour cell lines; this processing was also preferentially observed within the caveolar fraction. Interestingly, whereas the expression of caveolin 1 had no effect on the MT1-MMP-dependent activation of proMMP-2, its co-expression with MT1-MMP antagonized the MT1-MMP-increased migratory potential of COS-7 cells. Taken together, our results provide evidence that MT1-MMP is preferentially compartmentalized and proteolytically processed in caveolae of cancer cells. The inhibition of MT1-MMP-dependent cell migration by caveolin 1 also suggests that the localization of MT1-MMP to caveolin-enriched domains might have an important function in the control of its enzymic activity.
Annabi
B
B
Laboratoire de Médecine Moléculaire, Hôpital Sainte-Justine et Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, Québec, Canada H3C 3P8.
Lachambre
M
M
Bousquet-Gagnon
N
N
Pagé
M
M
Gingras
D
D
Béliveau
R
R
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002462:Cell Membrane / Q000201:enzymology; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D006868:Hydrolysis; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D017830:Octoxynol / Q000737:chemistry; D011994:Recombinant Proteins / Q000378:metabolism
D017931:DNA Primers; D018076:DNA, Complementary; D011994:Recombinant Proteins; D017830:Octoxynol; D020781:Matrix Metalloproteinase 1