in the tumor vascular volume at day 27 post-treatment. Representative tumor vascular volume and PSP maps are displayed in 5 Anti-Angiogenic Peptide for Breast Cancer Therapy the treatment resulted in a 60% increase of caspase-3 activity in the treated tumor sections compared to the control ones. This result was indicative of an increased apoptotic phenotype due to Anti-Angiogenic Peptide for Breast Cancer Therapy the treatment that could explain the significantly reduced tumor growth. Since in vitro treatment with the SP2024 peptide resulted in statistically significant inhibition of proliferation, adhesion and migration of LEC, we measured the effect of the peptide on the lymphatic vessels in the MDA-MB-231 treated tumor by staining for the molecular marker LYVE-1 in the excised tumor 
sections. Discussion In the present study, we investigated the effect of an antiangiogenic PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19691102/ peptide on tumor progression. This peptide is an optimized version of a peptide derived from the non-collagenous domain of collagen IV. The replacement of the two cysteine residues by isoleucine resulted in greater solubility, stability and activity over the parent peptide. We studied the effect of the modified SP2024 peptide on tumor growth by treating MDA-MB231 tumor bearing mice daily with i.p. injections, and we observed an inhibition of tumor growth. To understand the mechanism of action of the peptide, we investigated its effect on several processes that are critical for tumor progression, and found that the peptide significantly inhibited proliferation, migration and adhesion not only of vascular cells, but also of tumor cells. We then showed that this inhibition was mediated via the VEGFR2 pathway by demonstrating inhibition of phosphorylation of VEGFR2 in the 1702259-66-2 biological activity presence of the peptide and that of a downstream molecule PLCc in endothelial cells, while in cells which do not express VEGFR2 in vitro such as MDA-MB-231, the effects shown in Anti-Angiogenic Peptide PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19689163 for Breast Cancer Therapy Since this peptide is derived from collagen IV, we also investigated its effect on the expression of other extracellular proteins, such as collagen I, and found no significant effect. Our study showed that the SP2024 peptide is a strong candidate for cancer therapy owing to its multimodal activity. By inhibiting the proliferation, adhesion and migration of vascular and lymphatic endothelial cells, the peptide caused a reduction in microvascular and lymphatic vessel densities. Combined with its anti-tumorigenic effects, the treatment resulted in an inhibition of tumor growth in vivo. Moreover, the treatment affected, specifically, the neovasculature and not the established vasculature, as demonstrated by the absence of decrease in the vasculature of muscle tissue from treated mice, making the SP2024 peptide a promising candidate for anti-angiogenic therapy in breast cancer. Anti-angiogenic therapies have not yet fulfilled the hopes that existed at their discovery, partly due to the inability to monitor their activity over the course of the treatment. Implementing a monitoring regimen as described in this study would allow physicians to adjust the dose or frequency of the treatment in the future, which might increase the success and efficacy of such therapies. adhesion, and migration of endothelial and tumor cells. In vivo studies showed a significant growth inhibition of triple negative MDA-MB-231 xenografts. Changes in vascular properties throughout the treatment were monitored