Journal
ANGIOGENESIS
Volume 18, Issue 1, Pages 31-46Publisher
SPRINGER
DOI: 10.1007/s10456-014-9445-2
Keywords
Angiogenesis; Integrin; MMPs; Melanoma; p38 MAPK; Insulin; like growth factor; IGFBP-4
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A more complete understanding of the mechanisms that regulate the angiogenic switch, which contributes to the conversion of small dormant tumors to actively growing malignancies, is important for the development of more effective anti-angiogenic strategies for cancer therapy. While significant progress has been made in understanding the complex mechanisms by which integrin alpha v beta 3 expressed in endothelial cells governs angiogenesis, less is known concerning the ability of alpha v beta 3 expressed within the tumor cell compartment to modulate the angiogenic output of a tumor. Here we provide evidence that alpha v beta 3 expressed in melanoma cells may contribute to the suppression of IGFBP-4, an important negative regulator of IGF-1 signaling. Given the multiple context-dependent roles for alpha v beta 3 in angiogenesis and tumor progression, our novel findings provide additional molecular insight into how alpha v beta 3 may govern the angiogenic switch by a mechanism associated with a p38 MAPK and matrix metalloproteinases-dependent regulation of the endogenous angiogenesis inhibitor IGFBP-4.
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