Angiomotin expression promotes hemangioendothelioma invasion

Levchenko, Tetyana; Bratt, Anders; Arbiser, Jack L.; Holmgren, Lars

doi:10.1038/sj.onc.1207264

Cited by 45 publications

(53 citation statements)

References 24 publications

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“…Moreover, transgenic mice expressing this same mutated form of angiomotin died at embryonic day 9.5 with evidence of nonmigration of EC into the neuroectoderm and intersomitic regions. Finally, exogenous expression of human angiomotin in EC resulted in stabilization of established tubes for over 30 days, as well as evidence of enhanced invasion of EC derived from these tubes [Levchenko et al, 2004].…”

Section: Cell Surface Target: Angiomotinmentioning

confidence: 95%

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

Wahl

Kenan

Gonzalez-Gronow

et al. 2005

J of Cellular Biochemistry

114

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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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Section: Cell Surface Target: Angiomotinmentioning

confidence: 95%

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

Wahl

Kenan

Gonzalez-Gronow

et al. 2005

J of Cellular Biochemistry

114

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“…Other receptors for angiostatin have also been identified: for example, ATP synthase, the integrin ␣ v ␤ 3 , and c-Met (16). Amot is a membraneassociated protein that mediates angiostatin inhibition of endothelial migration and tube formation in vitro (17)(18)(19)(20). A role of Amot in cell motility is also indicated by the finding that Amot-deficient mouse embryos exhibit a migratory defect in the anterior visceral endoderm at embryonic day 7.5 (21).…”

mentioning

confidence: 85%

A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth

Holmgren

Ambrosino

Birot

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Endogenous angiogenesis inhibitors have shown promise in preclinical trials, but clinical use has been hindered by low half-life in circulation and high production costs. Here, we describe a strategy that targets the angiostatin receptor angiomotin (Amot) by DNA vaccination. The vaccination procedure generated antibodies that detected Amot on the endothelial cell surface. Purified Ig bound to the endothelial cell membrane and inhibited endothelial cell migration. In vivo, DNA vaccination blocked angiogenesis in the matrigel plug assay and prevented growth of transplanted tumors for up to 150 days. We further demonstrate that a combination of DNA vaccines encoding Amot and the extracellular and transmembrane domains of the human EGF receptor 2 (Her-2)͞neu oncogene inhibited breast cancer progression and impaired tumor vascularization in Her-2͞neu transgenic mice. No toxicity or impairment of normal blood vessels could be detected. This work shows that DNA vaccination targeting Amot may be used to mimic the effect of angiostatin.cancer vaccines ͉ neoplasia ͉ neovascularization ͉ breast cancer ͉ angiostatin

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“…In vitro experiments indicate that Amot promotes migration and tube formation of endothelial cells (Troyanovsky et al, 2001). Interestingly, AMOT is involved in invasion of tumor cells by promoting angiogenesis (Levchenko et al, 2004), and higher levels of AMOT transcripts are detected in human breast tumor tissues (Jiang et al, 2006). The expression of Amot is restricted to angiogenic vessels of lobular mammary carcinoma developed in Her-2/neu transgenic mice, and thus Amot can serve as a target for anti-angiogenic therapy .…”

Section: Introductionmentioning

confidence: 99%

Amotl2 is essential for cell movements in zebrafish embryo and regulates c-Src translocation

Huang

Jia

et al. 2007

Development

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Angiomotin (Amot), the founding member of the Motin family, is involved in angiogenesis by regulating endothelial cell motility, and is required for visceral endoderm movement in mice. However, little is known about biological functions of the other two members of the Motin family, Angiomotin-like1 (Amotl1) and Angiomotin-like2 (Amotl2). Here, we have identified zebrafish amotl2 as an Fgf-responsive gene. Zebrafish amotl2 is expressed maternally and in restricted cell types zygotically. Knockdown of amotl2 expression delays epiboly and impairs convergence and extension movement, and amotl2-deficient cells in mosaic embryos fail to migrate properly. This coincides with loss of membrane protrusions and disorder of F-actin. Amotl2 partially co-localizes with RhoB-or EEA1-positive endosomes and the non-receptor tyrosine kinase c-Src. We further demonstrate that Amotl2 interacts preferentially with and facilitates outward translocation of the phosphorylated c-Src, which may in turn regulate the membrane architecture. These data provide the first evidence that amotl2 is essential for cell movements in vertebrate embryos.

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Angiomotin expression promotes hemangioendothelioma invasion

Cited by 45 publications

References 24 publications

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

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

A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth

Amotl2 is essential for cell movements in zebrafish embryo and regulates c-Src translocation

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