™™| 09/06/10 | |||
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Technology name:
Technology description: VEGF-C is a member of the VEGF family of growth factors with both angiogenic and lymphangiogenic function. The role of VEGF-C in peritumor lymphatic remodeling and lymph node metastatic spread was demonstrated for multiple types of cancers. Clinically, high levels of VEGF-C were correlated with metastasis, low survival and poor prognosis. However, the molecular mechanism regulating VEGF-C expression has not been revealed. We found that lens epithelium-derived growth factor (LEDGF/p75), a recently discovered growth and survival transcriptional activator, regulates VEGF-C expression. LEDGF could thus provide a target for antimetastatic intervention.
We have disclosed a novel molecular mechanism regulating VEGF-C activity. VEGF-C expression was found to be induced in vitro and in vivo by the p75 splice variant of LEDGF. LEDGF/p75 conferred this activity upon binding to a specific stress response element (STRE), located in the VEGF-C gene. Moreover, ectopic LEDGF promoted tumor progression, as well as blood and lymph sprouting in two distinct in vivo tumor models. Fractal analysis of blood and lymphatic networks formed in tumors depicted that the over-expression of LEDGF gave rise to a significantly more complex vessel network than control tumors. Similarly, immuno-histochemical staining for specific blood and lymphatic endothelial cell markers resulted in a robust enhancement of both blood and lymphatic vessels, due to LEDGF over-expression.
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