Angiostatin induces endothelial cell apoptosis and activation of focal adhesion kinase independently of the integrin-binding motif RGD

Claesson‐Welsh, Lena; Welsh, Michael J.; Ito, Nobuyuki; Anand‐Apte, Bela; Söker, Shay; Zetter, Bruce R.; O’Reilly, Michael S.; Folkman, Judah

doi:10.1073/pnas.95.10.5579

Cited by 318 publications

(219 citation statements)

References 19 publications

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“…Retrovirus-mediated expression of TIMP-3 in tumor cells inhib- 145 MMP-2 Various IFN-a 147 EC proliferation/migration Angiostatin 148,149 Various Endostatin 117,150 MT1-MMP, MMP-2 Various Arresten 151 EC proliferation, migration Canstatin 152 EC viability, migration Tumstatin 153,154 EC viability, migration, protein synthesis Platelet factor 4 155 VEGF and bFGF signaling TIMP-1 156 Broad-range Various effects, including MMP inhibition TIMP-2 157 Broad-range Various effects, including MMP inhibition TIMP-3 138 Broad-range Various effects, including MMP inhibition TIMP-4 136 Broad-range Various effects, including MMP inhibition Exogenous/synthetic TNP-470 158 EC proliferation Squalamine 159 EC proliferation Captopril 160 MMP-2, MMP-9 EC migration Combretastatin-A4 161 EC tubulin CP-547, 632 162 VEGFR-2 and bFGF kinases Vitaxin 163 a v b 3 integrin, EC apoptosis EMD121974 164 a v b 3 and a v b 5 integrin COL-3 83 MMP-2, -9, -14 MMPs Neovastat 165,166 MMP-2, -9, -12 MMPs, designed to avoid sheddases BMS-275291 54 MMP-1, -2, -3, -7, -9, -14 Bevacizumab 167 VEGF ited tumor growth and angiogenesis in vivo. Tumors overexpressing TIMP-3 failed to form a functional vasculature and had reduced pericyte recruitment.…”

Section: Timps As Potential Antiangiogenic Agentsmentioning

confidence: 99%

Metalloproteinases and their inhibitors in tumor angiogenesis

Handsley

Edwards

2005

Intl Journal of Cancer

259

211

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Angiogenesis is the process by which new blood vessels are formed from preexisting vasculature. It is an essential feature of the female reproductive cycle, embryonic development and wound repair. Angiogenesis has also been identified as a causal or contributing factor in several pathologies, including cancer, where it is a rate-limiting step during tumor progression. Matrix metalloproteinases (MMPs) are a family of soluble and membrane-anchored proteolytic enzymes that can degrade components of the extracellular matrix (ECM) as well as a growing number of modulators of cell function. Several of the MMPs, in particular the gelatinases and membrane-type 1 MMP (MT1-MMP), have been linked to angiogenesis. Potential roles for these proteases during the angiogenic process include degradation of the basement membrane and perivascular ECM components, unmasking of cryptic biologically relevant sites in ECM components, modulation of angiogenic factors and production of endogenous angiogenic inhibitors. This review brings together what is currently known about the functions of the MMPs and the closely related ADAM (a disintegrin and metalloproteinase domain) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) families in angiogenesis and considers how this information might be useful in manipulation of the angiogenic process, with a view to constraining tumor progression. ' 2005 Wiley-Liss, Inc.Key words: metalloproteinase; tumor; angiogenesis; tissue inhibitor of metalloproteinases; protease; extracellular matrix Angiogenesis is an essential feature of several physiologic processes such as the developmental growth of organs, wound healing and the female reproductive cycle. 1 It is also particularly significant in cancer progression, being a crucial step in the transition of a tumor from a hyperplastic but contained in situ state to a malignant phenotype. 2,3 To allow its growth beyond a certain critical size, a solid avascular tumor must develop its own blood supply in order to meet its growing metabolic requirements. 1 Vascularization of a tumor also provides a route for dissemination of the tumor cells to different sites around the body.Although angiogenesis appears to be the primary form of tumor vascularization, the malignant cells of a tumor can gain access to a blood supply through other means, such as via tumor-induced vasculogenesis, in which bone marrow-derived precursor endothelial cells contribute to the formation of tumor vessels. 4,5 Vasculogenic mimicry is another form of vessel formation that has been reported in certain tumor types, such as aggressive human uveal melanomas, prostate and breast tumors. [6][7][8] In these cases, networks of tumor cell-lined vascular channels were identified within the tumors. Finally, vessel co-option, implemented by tumor cells as a temporary means of gaining access to a blood supply, involves the tumor cells growing around and thus co-opting existing host vessels to form an initially well-vascularized tumor. 9 This review will highlight new insigh...

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Section: Timps As Potential Antiangiogenic Agentsmentioning

confidence: 99%

Metalloproteinases and their inhibitors in tumor angiogenesis

Handsley

Edwards

2005

Intl Journal of Cancer

259

211

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“…NHE, pH dependent signal transduction to the cytoskeleton, and angiostatin. It has been reported that angiostatin treatment catalyzes FAK phosphorylation in the absence of integrin clustering [Claesson-Welsh et al, 1998]. Integrin clustering is required for cell attachment to substrate.…”

Section: Other Factors Affecting Regulation Ofmentioning

confidence: 99%

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

Wahl

Kenan

Gonzalez-Gronow

et al. 2005

J of Cellular Biochemistry

113

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Tumor growth requires the development of new vessels that sprout from pre-existing normal vessels in a process known as ''angiogenesis'' [Folkman (1971) N Engl J Med 285:1182-1186. These new vessels arise from local capillaries, arteries, and veins in response to the release of soluble growth factors from the tumor mass, enabling these tumors to grow beyond the diffusion-limited size of approximately 2 mm diameter. Angiostatin, a naturally occurring inhibitor of angiogenesis, was discovered based on its ability to block tumor growth in vivo by inhibiting the formation of new tumor blood vessels [O'Reilly et al. (1994a) Cold Spring Harb Symp Quant Biol 59:471-482]. Angiostatin is a proteolytically derived internal fragment of plasminogen and may contain various members of the five plasminogen ''kringle'' domains, depending on the exact sites of proteolysis. Different forms of angiostatin have measurably different activities, suggesting that much remains to be elucidated about angiostatin biology. A number of groups have sought to identify the native cell surface binding site(s) for angiostatin, resulting in at least five different binding sites proposed for angiostatin on the surface of endothelial cells (EC). This review will consider the data supporting all of the various reported angiostatin binding sites and will focus particular attention on the angiostatin binding protein identified by our group: F 1 F O ATP synthase. There have been several developments in the quest to elucidate the mechanism of action of angiostatin and the regulation of its receptor. The purpose of this review is to describe the highlights of research on the mechanism of action of angiostatin, its' interaction with ATP synthase on the EC surface, modulators of its activity, and issues that should be explored in future research related to angiostatin and other anti-angiogenic agents.

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“…Finally, angiostatin-induced endothelial cell apoptosis (Claesson-Welsh et al, 1998;Lucas et al, 1998) paradoxically involves FAK activation (Claesson-Welsh et al, 1998). FAK activation by angiostatin is not associated with Src coactivation and does not involve integrin signalling.…”

Section: Apoptotic Pathwaysmentioning

confidence: 99%

Apoptosis in the vasculature: mechanisms and functional importance

Mallat¹,

Tedgui²

2000

British J Pharmacology

301

213

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Apoptotic death has now been recognized in a number of common and threatening vascular diseases, including atherosclerosis. Interest in apoptosis research relates to the fact that apoptosis, in contrast to oncosis, is a highly regulated process of cell death which raises the hope for the development of speci®c therapeutic strategies to alter disease progression. This review summarizes the mechanisms involved in vascular endothelial and smooth muscle cell survival/apoptosis, and the potential roles of apoptotic death in atherosclerosis and restenosis. The potential e ects of modulation of apoptosis in these diseases are also discussed.

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Angiostatin induces endothelial cell apoptosis and activation of focal adhesion kinase independently of the integrin-binding motif RGD

Cited by 318 publications

References 19 publications

Metalloproteinases and their inhibitors in tumor angiogenesis

Metalloproteinases and their inhibitors in tumor angiogenesis

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

Apoptosis in the vasculature: mechanisms and functional importance

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