A Mechanism for Modulation of Cellular Responses to VEGF

Byzova, Tatiana V.; Goldman, Corey K.; Pampori, Nisar A.; Thomas, Kenneth A.; Bett, Andrew J.; Shattil, Sanford J.; Plow, Edward F.

doi:10.1016/s1097-2765(05)00076-6

Cited by 59 publications

(45 citation statements)

References 36 publications

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“…Because ShcA is recruited by the cytosolic tails of integrins (60,68,69) as well as by Ang-1-activated Tie2, it is stimulating to hypothesize that this adaptor integrates signals coming from these receptors leading to capillary sprouting. In this respect, a strict cooperation between ␣ v ␤ 3 integrin and tyrosine kinase vascular endothelial growth factor receptor-2 has been proposed as an important mean to regulate migratory response of ECs at the tip of sprouting vessels (70,71).…”

Section: Discussionmentioning

confidence: 99%

“…For instance, vascular endothelial growth factor receptor 2-mediated activation of PI 3-kinase results in migration or survival. These activities are reciprocally exclusive and depend on the association of the receptor with ␣ v ␤ 3 integrin or VE-cadherin with ␣ v ␤ 3 integrin being permissive for endothelial motility and VE-cadherin being permissive for survival (70,71,77,78). Therefore, a possibility is that Tie2 forms complexes with other transmembrane proteins, which contribute in the different assembly of cytoplasmic transduceosome (79) including the modulation of SchA-mediated effects.…”

Section: Discussionmentioning

confidence: 99%

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Adaptor ShcA Protein Binds Tyrosine Kinase Tie2 Receptor and Regulates Migration and Sprouting but Not Survival of Endothelial Cells

Audero

Cascone

Maniero

et al. 2004

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Adaptor ShcA Protein Binds Tyrosine Kinase Tie2 Receptor and Regulates Migration and Sprouting but Not Survival of Endothelial Cells

Audero

Cascone

Maniero

et al. 2004

Journal of Biological Chemistry

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“…Cell migration assays in transwell plates (8-m pore size) were performed as described (7). Soft agar assay was performed as described (8).…”

Section: Analysis Of In Vivo Tumormentioning

confidence: 99%

“…The intricacies of angiogenesis and tumor growth seem to be coordinated by cross-talk between VEGF, its receptors, and integrins (4). Several integrins are known to modulate VEGF͞ VEGF receptor (VEGFR) signaling (5,6), whereas VEGF, acting primarily through VEGFR2, directly controls the functional activity of integrins (7,8). Although recent studies emphasize the role of integrin ␣v␤3 as a ''gatekeeper'' of VEGF-mediated processes (9)(10)(11), the mechanisms involved in this interdependency remain elusive.…”

mentioning

confidence: 99%

VEGF–integrin interplay controls tumor growth and vascularization

Razorenova

McCabe

et al. 2005

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

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169

109

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Cross-talk between the major angiogenic growth factor, VEGF, and integrin cell adhesion receptors has emerged recently as a critical factor in the regulation of angiogenesis and tumor development. However, the molecular mechanisms and consequences of this intercommunication remain unclear. Here, we define a mechanism whereby integrin ␣v␤3, through activation, clustering, and signaling by means of p66 Shc (Src homology 2 domain containing), regulates the production of VEGF in tumor cells expressing this integrin. Tumors with ''activatable'' but not ''inactive'' ␤3 integrin secrete high levels of VEGF, which in turn promotes extensive neovascularization and augments tumor growth in vivo. This stimulation of VEGF expression depends upon the ability of ␣v␤3 integrin to cluster and promote phosphorylation of p66 Shc. These observations identify a link between ␤3 integrins and VEGF in tumor growth and angiogenesis and, therefore, may influence anti-integrin as well as anti-VEGF therapeutic strategies.activation ͉ angiogenesis ͉ Src homology 2 domain containing

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“…Changes in migratory functions can be induced by growth factors and altered production and activity of matrix-degrading enzymes, such as metalloproteinases. Connections between these phenomena and integrin function are just beginning to emerge (3,(16)(17)(18). Here, we asked whether and how the activation state of tumor cell integrin ␣v␤3 helps to regulate breast cancer cell migration.…”

mentioning

confidence: 99%

Activated integrin αvβ3 cooperates with metalloproteinase MMP-9 in regulating migration of metastatic breast cancer cells

Rolli

Fransvea

Pilch

et al. 2003

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

288

250

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Expression of adhesion receptor integrin ␣v␤3 in an activated functional form strongly promotes metastasis in human breast cancer cells. Here, we report that ␣v␤3 cooperates with matrix metalloproteinase type 9 (MMP-9) in breast cancer cell migration. This cooperation is regulated by the activation state of the integrin. Expression of activated ␣v␤3 in metastatic variants of MDA-MB 435 human breast cancer cells and primary metastatic cells from breast cancer patients strongly enhanced migration toward vitronectin and fibrinogen. This enhancement was mediated by a soluble factor produced by breast cancer cells expressing activated ␣v␤3. When transferred, this factor also up-regulated ␣v␤3-dependent migration of breast cancer cells that express the nonactivated integrin. The factor was identified as metalloproteinase MMP-9. Whereas all tested breast cancer cell variants produced latent MMP-9, only those with activated ␣v␤3 produced the mature form of this metalloproteinase. Recombinant mature MMP-9, but not latent MMP-9 or either form of MMP-2, enhanced ␣v␤3-dependent breast cancer cell migration. The migratory response was inhibited by tissue inhibitors of metalloproteinase or when MMP-9 was depleted from the inducing supernatants. The results indicate a causal relationship between the expression of activated integrin ␣v␤3 and production of enzymatically active MMP-9 in metastatic breast cancer cells. These molecules cooperate to enhance breast cancer cell migration toward specific matrix proteins, and this may contribute to the strongly enhanced metastatic capacity of breast cancer cells that express activated ␣v␤3.M etastasis is the primary cause of death in breast cancer patients. Metastatic dissemination depends on tumor cell adhesion, migration, and invasion. These steps involve integrins, a family of transmembrane adhesion receptors, composed of noncovalently linked ␣ and ␤ subunits (1). Integrins are known to exist in distinct states of activation, and these determine integrin functionality and affinity for ligands (2). For example, integrin activation controls which ligands are recognized, whether an integrin can support cell arrest under dynamic flow conditions or only stationary adhesion, and whether cells can migrate on or toward specific substrates (3). The importance of integrin activation has long been appreciated in leukocytes and platelets, where it controls inflammatory responses and thrombus formation (4, 5). Recent findings indicate that other cell types, such as endothelial cells and tumor cells, can also regulate their interaction with extracellular matrix proteins by integrin activation (6-9). This regulation may help to control angiogenesis and tumor metastasis.In breast and ovarian cancer, as well as in melanoma and glioma, malignant progression is associated with expression of tumor cell integrin ␣v␤3 (10-14). We recently found that ␣v␤3 can exist in human breast cancer cells in an activated or a nonactivated functional state. Only the activated state supports breast cancer cell arrest du...

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A Mechanism for Modulation of Cellular Responses to VEGF

Cited by 59 publications

References 36 publications

Adaptor ShcA Protein Binds Tyrosine Kinase Tie2 Receptor and Regulates Migration and Sprouting but Not Survival of Endothelial Cells

Adaptor ShcA Protein Binds Tyrosine Kinase Tie2 Receptor and Regulates Migration and Sprouting but Not Survival of Endothelial Cells

VEGF–integrin interplay controls tumor growth and vascularization

Activated integrin αvβ3 cooperates with metalloproteinase MMP-9 in regulating migration of metastatic breast cancer cells

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