The Embryonic Angiogenic Factor Del1 Accelerates Tumor Growth by Enhancing Vascular Formation

Aoka, Yoshikazu; Johnson, Frances L.; Penta, Kalyani; Hirata, Ken-ichi; Hidai, Chiaki; Schatzman, Randall C.; Varner, Judith A.; Quertermous, Thomas

doi:10.1006/mvre.2002.2414

Cited by 81 publications

(70 citation statements)

References 28 publications

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“…It is speculative that DEL-1 on tumor-exosomes is important for targeting exosomes to DC for cross-presentation. Recently, Aoka et al 61,62 suggested that DEL-1 acts as an angiogenic factor in the context of solid tumor formation and that the increase in vascular development accelerates tumor growth through decreased apoptosis. The role of DEL-1 in tumor exosomes can be bilateral first, attachment to dendritic cells and secondly, to increase the vascular development in the neighborhood of the tumor.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Exosomes Secreted by Human Mesothelioma Cells

Hegmans¹,

Bard²,

Hemmes³

et al. 2004

The American Journal of Pathology

308

233

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Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Exosomes Secreted by Human Mesothelioma Cells

Hegmans¹,

Bard²,

Hemmes³

et al. 2004

The American Journal of Pathology

308

233

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“…Zhong et al reported that Del1 can stimulate angiogenesis in animal models of ischemia (Zhong et al, 2003). Additionally, Del1 can accelerate tumor growth by enhancing vascular formation (Aoka et al, 2002). Del1 has seemed to have ambiguous characteristics.…”

Section: E3 Induces Apoptosismentioning

confidence: 99%

Improvement of FasL Gene Therapy In Vitro by Fusing the FasL to Del1 Protein Domains

Kitano¹,

Mamiya²,

Hidai³

2011

Targets in Gene Therapy

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“…In the adult, Hox D3 is expressed in vascular endothelium in response to angiogenic growth factors, such as bFGF and Del-1, in healing wounds, and in tumors (27). This transcription factor subsequently promotes expression of several genes associated with the angiogenic phenotype including cyclin D1, integrin ␣ v ␤ 3 , and uPA (25,26,28,(32)(33)(34). When overexpressed in vivo, Hox D3 promotes a hemangioma-like proliferation of blood vessels (25,28).…”

mentioning

confidence: 99%

The Homeobox Transcription Factor Hox D3 Promotes Integrin α5β1 Expression and Function during Angiogenesis

Boudreau

Varner

2004

Journal of Biological Chemistry

Self Cite

129

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Neovascularization promotes wound healing, tumor growth, and arthritis. Endothelial cell migration and survival during neovascularization are regulated by adhesion proteins, including integrin ␣ 5 ␤ 1 . Integrin ␣ 5 ␤ 1 is poorly expressed on normal quiescent blood vessels, but its expression is induced on tumor blood vessels and in response to angiogenic factors such as basic fibroblast growth factor, interleukin-8, tumor necrosis factor-␣, and the angiomatrix protein Del-1. We show here that ␣ 5 ␤ 1 expression, and hence function, during angiogenesis is regulated by the transcription factor Hox D3, a homeobox gene that also controls the expression of endothelial cell integrin ␣ v ␤ 3 and urokinase-type plasminogen activator. Hox D3 expression in endothelial cells enhances integrin ␣ 5 protein and message expression, whereas Hox D3 antisense inhibits its expression. Hox D3 promotes ␣ 5 expression during angiogenesis in vivo, whereas inhibition of ␣ 5 expression by Hox D3 antisense suppresses angiogenesis. Hox D3 binds directly to the promoters of the integrin ␣ 5 and ␤ 3 subunits, inducing subunit expression. As Hox D3, integrin ␣ v ␤ 3 , and integrin ␣ 5 ␤ 1 are expressed on tumor blood vessels but not on normal quiescent vessels, these studies suggest that Hox D3 coordinately regulates the expression of integrin ␣ 5 ␤ 1 and integrin ␣ v ␤ 3 during angiogenesis in vivo. These studies also suggest that Hox D3 inhibition could be a useful approach to inhibit tumor angiogenesis.Angiogenesis, the formation and differentiation of blood vessels from pre-existing vessels or endothelial progenitor cells, is important in both health and disease (1-6). Neovascularization is an important process during embryonic development, wound healing, and reproduction. It also plays an important role in the development of tumors and other diseases such as diabetic retinopathy, age-related macular degeneration, and psoriasis (1-6). Because neovascularization promotes cancer and other diseases, it is important to gain an understanding of the mechanisms by which angiogenesis is regulated.The integrin family of cell adhesion proteins mediates cell attachment to the extracellular matrix and promotes the survival, proliferation, and motility of ECs 1 during angiogenesis (7-18). In fact, at least three integrins receptors for provisional matrix proteins (␣ v ␤ 3 , ␣ v ␤ 5 , and ␣ 5 ␤ 1 ) play important roles in angiogenesis (10, 12, 13, 16 -22). Integrin ␣ 5 ␤ 1 plays a key role in the regulation of angiogenesis, as antagonists of this integrin inhibit angiogenesis (12,16,17). Both ␣ 5 ␤ 1 and its ligand fibronectin are poorly expressed in quiescent endothelium but strongly expressed in proliferating endothelium (16). Expression of integrin ␣ 5 ␤ 1 is up-regulated on human tumor vasculature in breast and colon tumors (16). It is also up-regulated on blood vessels in the brain during wound healing (19). Once expressed, ␣ 5 ␤ 1 regulates the survival and migration of endothelial cells in vitro and in vivo (12,17). Loss of the gene encoding t...

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The Embryonic Angiogenic Factor Del1 Accelerates Tumor Growth by Enhancing Vascular Formation

Cited by 81 publications

References 28 publications

Proteomic Analysis of Exosomes Secreted by Human Mesothelioma Cells

Proteomic Analysis of Exosomes Secreted by Human Mesothelioma Cells

Improvement of FasL Gene Therapy In Vitro by Fusing the FasL to Del1 Protein Domains

The Homeobox Transcription Factor Hox D3 Promotes Integrin α5β1 Expression and Function during Angiogenesis

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