Abstract
Desmogleins (Dsg2) are the major components of desmosomes. Dsg2 has five extracellular tandem cadherin domains (EC1-EC5) for cell-cell interaction. We had previously confirmed the Dsg2 antibody and its epitope (named KC21) derived from EC2 domain suppressing epithelial-mesenchymal transition and invasion in human cancer cell lines. Here, we screened six peptide fragments derived from EC2 domain and found that KR20, the parental peptide of KC21, was the most potent one on suppressing endothelial colony-forming cell (ECFC) tube-like structure formation. KC21 peptide also attenuated migration but did not disrupt viability and proliferation of ECFCs, consistent with the function to inhibit VEGF-mediated activation of p38 MAPK but not AKT and ERK. Animal studies showed that KC21 peptides suppressed capillary growth in Matrigel implant assay and inhibited oxygen-induced retinal neovascularization. The effects were comparable to bevacizumab (Bev). In conclusion, KC21 peptide is an angiogenic inhibitor potentially useful for treating angiogenesis-related diseases.
Highlights
Desmosomes provide strong adhesion to maintain tissue function and organ architecture
Mutations of Dsg2 are detected in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) [8], and expression of Dsg2 is increased in several epithelialderived malignancies including basal-cell carcinomas, squamous cell carcinomas, and metastatic prostate cancer [9,10,11]
Our study showed that the designed KC21 peptides have the ability to inhibit human endothelial colonyforming cells (ECFCs) migration in vitro, to reduce vascular endothelial growth factor (VEGF)-induced capillary growth and to suppress oxygen
Summary
Desmosomes provide strong adhesion to maintain tissue function and organ architecture. Chi-Sheng Lu and Yi-Nan Lee contributed to this work.
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