Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a lewis lung carcinoma

O’Reilly, Michael S.; Holmgren, Lars; Shing, Yuen; Chen, Catherine; Rosenthal, Robert W.; Moses, Marsha A.; Lane, William S.; Cao, Yihai; Sage, E. Helene; Folkman, Judah

doi:10.1016/0092-8674(94)90200-3

Cited by 3,071 publications

(2,019 citation statements)

References 48 publications

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“…54,55 All current treatments (surgical, laser and photodynamic therapy) merely delay severe vision loss, because they are directed at destroying new vessels but do not address the underlying angiogenic stimuli that frequently cause recurrences. 56 Currently, there are no antiangiogenic treatments available for patients with ocular neovascularization, but several new approaches such as intraocular injections of an aptamer that binds VEGF or an anti-VEGF antibody 57 or proteins with antiangiogenic activity [58][59][60] are being considered. Recombinant AAVmediated gene transfer offers an alternative for local sustained delivery of antiangiogenic proteins to intraocular tissues.…”

Section: Gene Transfer In Animal Models Of Retinal Degenerationmentioning

confidence: 99%

Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives

Rolling

2004

Gene Ther

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Section: Gene Transfer In Animal Models Of Retinal Degenerationmentioning

confidence: 99%

Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives

Rolling

2004

Gene Ther

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“…Immunoprecipitations were carried out as described in Materials and methods b1 integrins and metastasis C Brakebusch et al primary tumor, e.g. by angiostatin (O'Reilly et al, 1994).…”

Section: Attachment Of Germ 11 and Germ 116 Cells To Ecm Proteinsmentioning

confidence: 99%

β1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts

Brakebusch

Wennerberg

Krell³

et al. 1999

Oncogene

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To investigate the role of b1 integrin during tumor metastasis, we established a ras-myc transformed ®broblastoid cell line with a disrupted b1 integrin gene on both alleles (GERM 11). Stable transfection of this cell line with an expression vector encoding b1A integrin resulted in b1A integrin-expressing sublines. Tumors were induced by subcutaneous injection of GERM 11 cells and 3 independent b1 integrin expressing sublines (GERM 116, 1A10, 2F2) into syngeneic mice. After 10 days tumors were surgically removed. While average weights of GERM 11 and GERM 116 tumors were similar, tumors induced by the high expressing clones 1A10 and 2F2 were markedly smaller, suggesting an inverse correlation of tumor growth and b1 integrin expression. The metastasis potential of all three b1 integrin-expressing GERM 11 sublines tested was signi®cantly higher than that of the b1-de®cient GERM 11 cells. GERM 116 tumors led in all animals to severe metastasis in lung and liver, while GERM 11 tumors induced only a few metastatic foci in the lung. Stroma of both tumors contained nidogen and high amounts of tenascin C, but only a few very low levels of ®bronectin, laminin-1, and collagen type I. b1 integrin, therefore, increases but is not essential for metastasis of ras-myc transformed ®broblasts.

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“…7 Angiostatin has been described to exert potent antiangiogenic and antitumor activities in a variety of murine tumor models. [7][8][9][10] Similarly, a 20-kDa (184 amino acid (aa)) C-terminal fragment of collagen XVIII, termed endostatin (ES), is reported to be a potent inhibitor of tumor angiogenesis and micrometastases development. 5,11 The urokinase plasminogen activator (uPA) binds to its receptor uPAR via its light chain fragments, 12 known as amino-terminal fragment ATF (residues .…”

Section: Introductionmentioning

confidence: 99%

A gene transfer comparative study of HSA-conjugated antiangiogenic factors in a transgenic mouse model of metastatic ocular cancer

et al. 2006

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Different antiangiogenic and antimetastatic recombinant adenoviruses were tested in a transgenic mouse model of metastatic ocular cancer (TRP1/SV40 Tag transgenic mice), which is a highly aggressive tumor, developed from the pigmented epithelium of the retina. These vectors, encoding amino-terminal fragments of urokinase plasminogen activator (ATF), angiostatin Kringles (K1-3), endostatin (ES) and canstatin (Can) coupled to human serum albumin (HSA) were injected to assess their metastatic and antiangiogenic activities in our model. Compared to AdCO1 control group, AdATF-HSA did not significantly reduce metastatic growth. In contrast, mice treated with AdK1-3-HSA, AdES-HSA and AdCan-HSA displayed significantly smaller metastases (1.1971.19, 0.8771.5, 0.4370.56 vs controls 4.0475.12 mm 3 ). Moreover, a stronger inhibition of metastatic growth was obtained with AdCan-HSA than with AdK1-3-HSA (P ¼ 0.04). Median survival was improved by 4 weeks. A close correlation was observed between the effects of these viruses on metastatic growth and their capacity to inhibit tumor angiogenesis. Our study indicates that systemic antiangiogenic factors production by recombinant adenoviruses, particularly Can, might represent an effective way of delaying metastatic growth via inhibition of angiogenesis.

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Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a lewis lung carcinoma

Cited by 3,071 publications

References 48 publications

Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives

Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives

β1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts

A gene transfer comparative study of HSA-conjugated antiangiogenic factors in a transgenic mouse model of metastatic ocular cancer

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