作者: Oliver Stoeltzing , Niels Reinmuth , Corazon D. Bucana , Jane S. Wey , Wenbiao Liu
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摘要: Angiopoietin (Ang)-1 and -2 are critical regulators of embryonic postnatal neovascularization. Ang-1 activates the endothelial cell-specific tyrosine kinase receptor Tie-2, which in turn leads to enhanced cell survival stabilization. The effects on tumor angiogenesis remain controversial; although we have previously demonstrated that overexpression colon cancer cells a decrease s.c. growth, others shown may be proangiogenic. Few studies addressed role Angs tumors growing organ metastatic growth. We hypothesized inhibit growth cancers liver by inhibition angiogenesis. also wanted investigate mechanisms affects vivo. Human (HT29) were stably transfected with an construct or empty vector (pcDNA) injected directly into livers nude mice. After 37 days, harvested weighed, sizes measured. In additional experiment, validate paracrine effect Ang-1, various mixtures control Ang-1-transfected livers, was assessed. Direct recombinant studied vivo Gelfoam assay. impact vascular permeability investigated using intradermal Miles assay conditioned media from cells. Liver weights (P < 0.05), volumes vessel counts 0.01), proliferation 0.01) group significantly lower than those group. Tumor vessels developed higher degree pericyte coverage 0.02) pcDNA tumors. mixture even as few 1:10 cells/control resulted significant reduction hepatic 0.04). assay, implants decreased addition 0.01). Finally, medium more 0.05). Our results suggest is important regulator this secondary increasing periendothelial support Thus, could potentially serve antineoplastic anti-permeability agent for patients colorectal cancer.