. Author manuscript; available in PMC: 2015 Feb 1.

Published in final edited form as: Cytokine Growth Factor Rev. 2013 Nov 27;25(1):1–19. doi: 10.1016/j.cytogfr.2013.11.002

Table 1.

Multiple roles of proteases in VEGF-induced angiogenesis

System	Host^*	Enzyme	VEGF mRNA^†	VEGF Protein^†	VEGF Processing^†	Angiogenic Response^†	Pathogenesis ^†	Ref
*Proteases hinder vessel growth*
Breast tumor, T47D, subcutaneous	m/h	n.a.	n.a.	soluble VEGF ↑ relative to total VEGF	+ implied	↓ (instead enlargement)	↓	(13)

Oxygen-induced retinopathy	m	MMP12	Unch.	binding to vasculature ↑	+	↑ malformation	↑	(69)

Wound, chronic leg ulcer	h	Plasmin	↑	↓ VEGF₁₆₅	+	↓	↑	(104)
Wound, skin	m	Plasmin	n.a.	↓ VEGF₁₆₅ implied	+	↓	↑	(105)

*Proteases induce patent vessel growth*
Breast tumor	m	MMP9	Unch.	total VEGF Unch. ↓ gradient total VEGF VEGF-VEGFR2 ↑	–	↑	↑	(111)
	m/h	MMP9	n.a.	total VEGF Unch. VEGF-VEGFR2 ↑	n.a.	↑	↑	(137)

Cervical cancer	m	MMP9	n.a.	VEGF-VEGFR2 ↑	n.a.	↑	↑	(114)

Colon carcinoma (HT29) (ex vivo)	h	MMP9, 2, 8	n.a.	soluble VEGF₁₆₅ ↑ ↓ total HSPG	–	↑	Implied ↑	(77)
Colorectal cancer	h	MMP7	↑	n.a.	n.a.	↑	↑	(76)

Cornea	m	MMP7, 9, 2	↑	n.a.	n.a.	↑	↑	(93)
Cornea	m	MMP9,2	↑	VEGF ↑	n.a.	↑	Implied ↑	(140)

Glioblastoma	m	MMP9	↑	% soluble VEGF ↑ total VEGF Unch. VEGF-VEGFR2 ↑	–	↑	Implied ↓	(113)

HUVEC migration and tube formation (in vitro)		MMP7	n.a.	VEGF₁₆₅ ↑	–	↑	n.a.	(78)

Ovarian tumor ascites (in vitro)	m/h	MMP2,9	n.a.	soluble VEGF ↑	–	↑ permeability	↑	(222)

Pancreatic islet	m	MMP9	Unch.	(ex vivo) soluble VEGF ↑ (in vivo) VEGF-VEGFR2 ↑	n.a.	↑	↑	(86)
	m	Heparanase	Unch.	VEGF-VEGFR2 ↑	n.a.	↑	↑	(109)

In vivo except where indicated.

Host organism; m = mouse; h = human; m/h = human tumor in mouse

^†

Arrows denote effect of protease-dependent state vs. control or protease-KO state; Unch = unchanged; n.a. = data not available.