Inhibitory Effect of Full-Length Human Endostatin on in Vitro Angiogenesis

Taddei, Letizia; Chiarugi, Paola; Brogelli, Laura; Cirri, Paolo; Magnelli, Lucia; Raugei, Giovanni; Ziche, Marina; Granger, Harris J.; Chiarugi, Vincenzo; Ramponi, Giampietro

doi:10.1006/bbrc.1999.1342

Cited by 67 publications

(57 citation statements)

References 22 publications

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“…Treatment of metatarsals with the 20 kDa angiostatic fragment of collagen 18 (endostatin) attenuated the formation of tubelike structures without affecting the formation of a feeder layer of fibroblast-like cells, underscoring the endothelial-specific properties of this angiostatic agent (Cao, 1998;O'Reilly et al, 1997;Taddei et al, 1999). This is in agreement with other recent studies in which the angiostatic effect of endostatin on endothelial cells was shown in vitro (Dhanabal et al, 1999a(Dhanabal et al, , 1999bYamaguchi et al, 1999) and in vivo (Dhanabal et al, 1999a;O'Reilly et al, 1997).…”

Section: Deckers Et Alsupporting

confidence: 87%

“…In contrast to recent observations by Kruger et al (2000) who used the human saphenous vein model and the rat aortic ring model, we did not detect a species difference in the antiangiogenic activity of endostatin. It should be noted that endothelial cells surrounding E17 metatarsals positively stained for collagen XVIII (own unpublished results), the endogenous source of mouse endostatin, which might explain the relatively high levels (5 g/ml) of this agent needed to block the angiogenic response as compared with other in vitro studies (Taddei et al, 1999;Yamaguchi et al, 1999). Although angiogenesis was inhibited by different classes of angiostatic agents, a small residual angiogenic activity was noticed.…”

Section: Deckers Et Almentioning

confidence: 91%

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Effect of Angiogenic and Antiangiogenic Compounds on the Outgrowth of Capillary Structures from Fetal Mouse Bone Explants

Deckers

Pluijm

Dooijewaard

et al. 2001

Laboratory Investigation

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SUMMARY:Fetal mouse metatarsals are well-known models to study cartilage differentiation and osteoclastic resorption. We show here the outgrowth of PECAM-1 positive tubelike structures from the bone rudiments. This feature can be used to study angiogenesis in vitro. The area of outgrowth significantly increased with culture time, as shown by computerized image analysis of PECAM-1 positive tubelike structures. Treatment with recombinant human vascular endothelial growth factor (rhVEGF-A) stimulated the formation of tubelike structures. Treatment of explants with the angiogenesis inhibitor endostatin, the chemokine IP-10, and the thalidomide derivative phatolyl glutamic acid (PG-acid) resulted in an inhibition of the formation of PECAM-1 positive tubelike structures of 48.8% (Ϯ 4%), 50.2% (Ϯ12%), and 80.8% (Ϯ3%), respectively. Outgrowth of tubelike structures was partly dependent on endogenous VEGF-A because treatment with anti-mVEGF-A and truncated VEGF receptor 1 (soluble fms-like tyrosine kinase 1, sFlt1) strongly inhibited the formation of tubelike structures 74% (Ϯ 4%) and 38% (Ϯ 5%), respectively. Neither onset of tube formation nor total area of tubelike structures were changed when metatarsals were cultured on a fibrin gel or collagen type I gel. Tube formation required activation of matrix metalloproteinases because treatment of the bones with an inhibitor of matrix metalloproteinases completely inhibited migration and tube formation, whereas treatment with an inhibitor of plasmin had no effect. In conclusion, we describe a new in vitro model to study angiogenesis that can be used to test the angiogenic or antiangiogenic potential of novel test compounds that also combines the multicellularity of in vivo assays with the accessibility and flexibility of in vitro assays. (Lab Invest 2001, 81:5-15).

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Section: Deckers Et Alsupporting

confidence: 87%

Section: Deckers Et Almentioning

confidence: 91%

Effect of Angiogenic and Antiangiogenic Compounds on the Outgrowth of Capillary Structures from Fetal Mouse Bone Explants

Deckers

Pluijm

Dooijewaard

et al. 2001

Laboratory Investigation

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“…It has been widely reported that endostatin has potent inhibitory effects on endothelial cell proliferation, migration, and tube formation [2,3] . Nucleolin, integrins, caveolin and clathrin have been demonstrated to mediate the anti-tumor effects of endostatin [4][5][6] .…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of PEGylated recombinant human endostatin (M2ES) in rats

Zuo-gang¹,

Jia²,

Guo

et al. 2015

Acta Pharmacol Sin

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Aim: M 2 ES is PEGylated recombinant human endostatin. In this study we investigated the pharmacokinetics, tissue distribution, and excretion of M 2 ES in rats. Methods: 125 I-radiolabeled M 2 ES was administered to rats by intravenous bolus injection at 3 mg/kg. The pharmacokinetics, tissue distribution and excretion of M 2 ES were investigated using the trichloroacetic acid (TCA) precipitation method. Results: The serum M 2 ES concentration-time curve after a single intravenous dose of 3 mg/kg in rats was fitted with a noncompartment model. The pharmacokinetic parameters were evaluated as follows: C max =28.3 μg·equ/mL, t 1/2 =71.5 h, AUC (0-∞) =174.6 μg·equ·h/mL, Cl=17.2 mL·h -1 ·kg -1 , MRT=57.6 h, and V ss =989.8 mL/kg for the total radioactivity; C max =30.3 μg·equ/mL, t 1/2 =60.1 h, AUC (0-∞) =146.2 μg·equ·h/mL, Cl=20.6 mL·h -1 ·kg -1 , MRT=47.4 h, and V ss =974.6 mL/kg for the TCA precipitate radioactivity. M 2 ES was rapidly and widely distributed in various tissues and showed substantial deposition in kidney, adrenal gland, lung, spleen, bladder and liver. The radioactivity recovered in the urine and feces by 432 h post-dose was 71.3% and 8.3%, respectively. Only 0.98% of radioactivity was excreted in the bile by 24 h post-dose. Conclusion: PEG modification substantially prolongs the circulation time of recombinant human endostatin and effectively improves its pharmacokinetic behavior. M 2 ES is extensively distributed in most tissues of rats, including kidney, adrenal gland, lung, spleen, bladder and liver. Urinary excretion was the major elimination route for M 2 ES.

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“…The endogenous antiangiogenic factors angiostatin and endostatin are proteolytic fragments of plasminogen and collagen VIII, respectively [88,89]. Angiostatin and endostatin inhibit proliferation and migration of endothelial cells, and induce endothelial cell apoptosis [88,[90][91][92][93][94]. Although the mechanism of action of endostatin is still unclear, the actions of angiostatin are most likely mediated via a cell surface ATP synthase [90].…”

Section: Antiangiogenic Factorsmentioning

confidence: 99%

Vascular Endothelial Growth Factor: Regulation in the Mouse Skin Carcinogenesis Model and Use in Antiangiogenesis Cancer Therapy

Conti

2002

The Oncologist

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Learning Objectives After completing this course, the reader will be able to: Describe mechanisms of tumor neovascularization. Identify possible targets for cancer therapy in the biologic pathways that control angiogenesis. Identify some of the drugs that are presently used in preclinical or clinical trials, as well as their targets. Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com Of the various mechanisms responsible for tumor neovascularization, the angiogenesis process, in particular vascular endothelial growth factor (VEGF), is described here as a target for cancer therapy. While hypoxia is a trigger of tumor angiogenesis, various alterations in oncogenes and tumor suppressor genes also have been reported to induce VEGF expression in tumors. The regulation of VEGF has been investigated in chemically induced mouse squamous cell carcinoma of the skin. In this cancer model, VEGF expression appears to be dependent on ras oncogene activation as well as the epidermal growth factor receptor. Thus, in addition to VEGF, oncogene signaling pathways may be relevant targets in antiangiogenesis cancer therapies. The central role of VEGF in angiogenesis has led to the development of several drugs targeting the pathway of this growth factor. The present paper provides an overview of these drugs and their stage of development. In the near future, clinical trials using anti‐VEGF drugs and other antiangiogenic agents, such as endostatin and angiostatin, will yield valuable information about their potential for cancer therapy.

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Inhibitory Effect of Full-Length Human Endostatin on in Vitro Angiogenesis

Cited by 67 publications

References 22 publications

Effect of Angiogenic and Antiangiogenic Compounds on the Outgrowth of Capillary Structures from Fetal Mouse Bone Explants

Effect of Angiogenic and Antiangiogenic Compounds on the Outgrowth of Capillary Structures from Fetal Mouse Bone Explants

Pharmacokinetics of PEGylated recombinant human endostatin (M2ES) in rats

Vascular Endothelial Growth Factor: Regulation in the Mouse Skin Carcinogenesis Model and Use in Antiangiogenesis Cancer Therapy

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