Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels

Brooks, Peter C.; Montgomery, Anthony M.P.; Rosenfeld, Mauricio; Reisfeld, Ralph A.; Hu, Tianhua; Klier, George; Cheresh, David A.

doi:10.1016/0092-8674(94)90007-8

Cited by 2,166 publications

(1,430 citation statements)

References 40 publications

Supporting

Mentioning

1,368

Contrasting

Unclassified

Order By: Relevance

“…Other integrins such as a v b 1 or a v b 3 and various b 1 integrins fail to rescue cells from apoptosis under these conditions. It is possible that under other conditions cells depend on other integrins for survival (Brooks et al, 1994;Boudreau et al, 1995). Di erent cell types may di er in their integrin dependence under the same conditions.…”

Section: Role Of Cell Shape In Anoikismentioning

confidence: 99%

“…Di erent cell types may di er in their integrin dependence under the same conditions. Thus vascular endothelial cells seem to depend on a v b 3 receptor for their survival (Brooks et al, 1994). Inhibition of a v b 3 function during angiogenesis with anti-a v b 3 antibodies both inhibited proliferation and induced apoptosis, whereas treatment with antibodies that block b 1 integrin function did not (Brooks et al, 1994).…”

Section: Role Of Cell Shape In Anoikismentioning

confidence: 99%

“…Thus vascular endothelial cells seem to depend on a v b 3 receptor for their survival (Brooks et al, 1994). Inhibition of a v b 3 function during angiogenesis with anti-a v b 3 antibodies both inhibited proliferation and induced apoptosis, whereas treatment with antibodies that block b 1 integrin function did not (Brooks et al, 1994). Similarly, prevention of interactions of mammary epithelium with the matrix by anti-b 1 integrin antibodies both inhibited proliferation and induced apoptosis (Boudreau et al, 1995).…”

Section: Role Of Cell Shape In Anoikismentioning

confidence: 99%

“…Several other integrin based drugs such as the peptides containing the integrin-binding RGD sequence (Ruoslahti, 1996), and mimics of such peptides that speci®cally block individual integrins are also under development. These drugs target thrombosis (a IIb b 3 in platelets (Pierschbacher et al, 1994), osteoporosis (a v b 3 in osteoclsts (Flores et al, 1992)) and tumor-induced angiogenesis (a v b 3 in neovascular endothelial cells (Brooks et al, 1994). In a recent exciting study, Ruoslahti's group used the in vivo selection of phage display libraries to isolate peptides that home speci®cally to tumor blood vessels.…”

Section: Summary and Therapeutic Applicationsmentioning

confidence: 99%

See 3 more Smart Citations

Signaling by integrin receptors

Kumar¹

1998

Oncogene

256

181

View full text Add to dashboard Cite

Adhesive interactions are critical for the proliferation, survival and function of all cells. Integrin receptors as the major family of adhesion receptors have been the focus of study for more than a decade. These studies have tremendously enhanced our understanding of the integrin-mediated adhesive interactions and have unraveled novel integrin functions in cell survival mechanisms and in the activation of divergent signaling pathways. The signals from integrin receptors are integrated from those originating from growth factor receptors in order to organize the cytoskeleton, stimulate cell proliferation and rescue cells from matrix detachment-induced programmed cell death. These functions are critical in the regulation of multiple processes such as tissue development, in¯ammation, angiogenesis, tumor cell growth and metastasis and programmed cell death.

show abstract

Section: Role Of Cell Shape In Anoikismentioning

confidence: 99%

Section: Role Of Cell Shape In Anoikismentioning

confidence: 99%

Section: Role Of Cell Shape In Anoikismentioning

confidence: 99%

Section: Summary and Therapeutic Applicationsmentioning

confidence: 99%

See 2 more Smart Citations

Signaling by integrin receptors

Kumar¹

1998

Oncogene

256

181

View full text Add to dashboard Cite

show abstract

“…7,8 The integrin -mediated interaction of the endothelial cells with the extracellular matrix supports migration and sustains survival of vascular cells in angiogenic blood vessels. 9,10 v 3 is up -regulated on cytokine -activated endothelial and smooth muscle cells as well as on vascular cells within tumors, whereas it is minimally expressed on quiescent vasculature. 5,10,11 Thus, v 3 is a suitable target molecule to inhibit angiogenesis.…”

mentioning

confidence: 99%

Inhibition of angiogenesis in vitro by αv integrin–directed antisense oligonucleotides

Kronenwett

Graf

Nedbal³

et al. 2002

Cancer Gene Ther

View full text Add to dashboard Cite

The integrin v 3 plays a central role in angiogenesis. In this study, we used antisense oligodeoxyribonucleotides ( ONs ) directed against the v subunit of v 3 to inhibit integrin expression. Ten ON sequences, which were selected by systematic alignment of computer -predicted secondary structures of v mRNA, were transfected into human umbilical vein endothelial cells ( HUVECs ). Following stimulation by PMA, five antisense ONs significantly inhibited v mRNA and protein expression in activated HUVEC at a concentration of 0.05 M with complete prevention of PMA -induced v up -regulation by the most potent antisense ON. Inhibition of v expression was associated with significant inhibition of migration of HUVEC by 28% and had no effect on proliferation and apoptosis. Moreover, transfection of antisense ON inhibited the formation of tube -like structures of HUVEC in Matrigel by 44%. In a cell culture model of angiogenesis consisting of a co -culture of endothelial cells with fibroblasts, transfection of antisense ONs resulted in an inhibition of tube formation of 61%. In conclusion, v antisense ONs are potent inhibitors of angiogenesis in vitro. They might, therefore, be a therapeutic alternative to antagonists, which directly bind to v integrins, and might be useful for the treatment of malignant tumors and hematological malignancies.

show abstract