GEP100-Arf6-AMAP1-Cortactin Pathway Frequently Used in Cancer Invasion Is Activated by VEGFR2 to Promote Angiogenesis
Figure 5
Blockage of pathologic angiogenesis by GEP100 siRNA and P4-TAT.
A, Immunohistochemistry of granulation tissue and scar tissue sections by use of the indicated antibodies. Bars, 100 µm. B–E, Effects of GEP100 siRNAs and P4-TAT (P4) on angiogenesis were measured using angioreactors implanted into nude mice, that contained basement membrane extracts and VEGF (500 ng ml−1) or MDA-MB-231 cells (1×105 cells); and amounts of Isolectin B4 accumulated within the basement membrane extracts were measured after incubation for 9 days. siRNAs, mixed with AteloGene at concentrations as indicated, were injected into mice at day 0 and day 4. TAT-peptides were added into angioreactors before implantation, at the indicated concentrations. An irrelevant RNA duplex (Irr) or a scrambled peptide (SC) was used as controls. Error bars show mean ± s.e.m., n = 8. * p<0.05. F–G, Effect of P4-TAT on CNV formation. Representative micrographs of CNV lesions in choroidal flatmounts from an animal treated with P4-TAT or SC. Red dashed line shows the extent of the CNV lesions filled with FITC-dextran. Scale bar, 100 µm. Quantitative analysis of the average CNV size is shown in G. Error bars show mean ± s.e.m., n = 70 to 77. *P<0.05.