New Strategies for the Next Generation of Matrix-Metalloproteinase Inhibitors: Selectively Targeting Membrane-Anchored MMPs with Therapeutic Antibodies

Table 1

Substrates for membrane-bound MMPs.

	Gene/Name	𝑀𝑟 latent	𝑀𝑟 active	Substrates
	MMP-14 (MT1-MMP)	66,000	56,000	Collagen I, II, III [34, 35], and IV [36–38], Gelatin, cartilage aggrecan, perlecan, fibronectin, vitronectin, nidogen, laminin, pro-TNF𝛼 [34, 35]; proMMP-2 [39]; proMMP-13 [40]; Galectin-3; MCP-3 [41]; SDF [42]; cell surface CD44 [43]; tTG [44].
Type I transmembrane MMPs	MMP-15 (MT2-MMP)	72,000	60,000	Gelatin; fibronectin; tenascin; nidogen; aggrecan; perlecan and laminin [35]; tTG [44]; proTNF𝛼 [35]; LRP (CD91) [45]; CXCL12 [46]; proMMP-2 [47].
	MMP-16 (MT3-MMP)	64,000	52,000	Native Collagen III, 𝛼2(I) collagen chain; cartilage proteoglycan; gelatin; casein; fibronectin; vitronectin; laminin-1; transferring; 𝛼1-proteinase inhibitor and 𝛼2-macroglobulin [48, 49]; tTG [44]; proMMP-2 [50].
	MMP-24 (MT5-MMP)	63,000	45,000	Fibronectin; Proteoglycans and cadherins [51, 52]; Gelatin; proMMP-2 and -9 [53, 54]; KISS-1 [55].
GPI-anchored MMPs	MMP-17 (MT4-MMP)	57,000	53,000	Gelatin [56]; alpha2-macroglobulin; ADAMTS-4; low density lipoprotein receptor related protein [57]; Fibrin/Fibrinogen; pro-TNF-alpha cleaved by mouse MMP-17 [58].
	MMP-25 (MT6-MMP)		56,000	Collagen IV; Gelatin; Fibrin/Fibrinogen [59, 60]; Fibronectin; laminin-1, alpha2-macroglobulin; ADAMTS-4; Chondroitin and dermatan sulfate proteoglycan; alpha1 proteinase inhibitor; urokinase plasminogen activator receptor, Galectin-3 [57].
Type II transmembrane MMPs	MMP-23	43,900	?	Unknown.

𝑀_𝑟: relative molecular mass.