Cancer Research
Research Toward a Cure
Angiogenesis
Angiogenesis—More examples from the literature:
Tumors require angiogenesis, the recruitment of new blood vessels, to supply oxygen and nutrients required for survival.
Angiogenesis can be activated by altering the balance of inducers and inhibitors that normally keep this process tightly regulated.
Endorepellin Binds and Downregulates the VEGF Receptor
Figure 1D and E. Levels of VEGFA after treatment with SHP-1 phosphatase inhibitor, measured with In-Cell Western™ assay. Inhibition of SHP-1 increases endogenous VEGFA levels. ICW assays were imaged with Odyssey® CLx.
Figure 1H and I. Changes in VEGFA levels were measured with quantitative Westerns, after treatment with endorepellin and a blocking antibody against α2β1. Blocking antibody attenuated the effects of endorepellin, confirming that α2β1 integrin is required for endorepellin activity. Fluorescent Westerns were imaged with Odyssey CLx.
Perlecan, which binds to the endothelial cell surface via integrins, may play a role in modulation of VEGF signaling. Endorepellin is a C-terminal angiostatic fragment of perlecan.
- Endorepellin binds α2β1 integrin and induces the SHP-1 tyrosine phosphatase, which inactivates VEGFR2 and several other receptor tyrosine kinases.
- Pulldown assays and cell-binding assays with IRDye® labeled endorepellin demonstrate that endorepellin binds directly to VEGF receptors 1 and 2. This interaction downregulates α2β1 and VEGFR2, concurrently activating SHP-1 and attenuating VEGFA transcription.
- Quantitative IR Western blots, In-Cell Western™ assays, and the Odyssey Imager were used to monitor changes in protein levels.
A Goyal, N Pal, M Concannon, M Paul, M Doran, C Poluzzi, K Sekiguchi, JM Whitelock, T Neill, and RV Iozzo. Endorepellin, the angiostatic module of perlecan, interacts with both the α2β1 integrin and vascular endothelial growth factor receptor 2 (VEGFR2): a dual receptor antagonism. J Biol Chem 286:25947-25962 (2011)
