Anti-integrins as a potential therapeutic target in angiogenesis

Mousa, Shaker A.

doi:10.1517/13543776.9.9.1237

Cited by 11 publications

(3 citation statements)

References 68 publications

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“…There are significant differences in endothelial cells, vessel wall and basal membrane between tumor and normal vasculature, during the tumor angiogenesis proceees (Bhutia and Maiti 2008;Mousa 1999). An example of this is the expression of the integrin avb3, it has been demonstrated that avb3 is preferentially expressed by the tumor vasculature but not by the normal vasculature.…”

Section: Discussionmentioning

confidence: 99%

“…These novel drugs usually target crucial signal transduction molecules or cell surface markers. As one of such kinds of molecules, integrin avb3 is important in angiogenesis and is over-expressed on the surface of various tumor cells during tumor progression and metastasis, while little is expressed on normal tissues (Mousa 1999;Miller et al 2000). The expression of avb3 is highly correlated with the degree of malignancy.…”

Section: Introductionmentioning

confidence: 99%

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An uPA cleavable conjugate of a recombinant αvβ3 targeting toxin and its bioactivity

Zhu

Zhou

Sun

2010

World J Microbiol Biotechnol

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Melittin is the predominant component of bee venom with cell membrane-disrupting capability. To release melittin on cell surfaces to destroy tumor cell membranes, we designed a recombinant targeting toxin with an uPA cleavable link. It contains A Disintegrin-like domain of ADAM 15 to selectively deliver fusion protein to the surface of the tumor cells expressing integrin avb3, a toxin domain consisting of four repeats of N-terminal 22 amino acids of melittin, and an uPA cleavable link in between. The fusion protein named as ADAM-Conj-Mel was successfully expressed in Escherichia coli and can be cleaved by uPA as well as conditioned medium of SW1990 tumor cells. In vitro, ADAM-Conj-Mel efficiently inhibits proliferation of human melanoma (C32) tumor cells. In vivo, it reduces B16 tumor volume by approximately 80%. Our data suggested that ADAM-Conj-Mel is a protein with potential in clinical development for cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An uPA cleavable conjugate of a recombinant αvβ3 targeting toxin and its bioactivity

Zhu

Zhou

Sun

2010

World J Microbiol Biotechnol

View full text Add to dashboard Cite

show abstract

“…In addition, tumour growth, resistance to chemotherapy, and metastasis, all involve integrin-mediated cellular and extracellular signalling pathways, wherein the up-regulation of integrin αVβ3 expression serves as an escape mechanism for tumours 21,22 . One of the ways to control the tumour progression has been to control angiogenesis via integrin antagonists [23][24][25][26][27] . The integrin antagonists that function effectively as anti-angiogenic agents were identified earlier 28 .…”

Section: Original Articlementioning

confidence: 99%