Anti-angiogenic treatment promotes triple-negative breast cancer invasion via vasculogenic mimicry

摘要: Agents that target angiogenesis have shown limited efficacy for human triple-negative breast cancer (TNBC) in clinical trials. Along with endothelium-dependent vessels, there is also vasculogenic mimicry (VM) the microcirculation of malignant tumors. The role VM not completely understood regarding anti-angiogenic treatment. In this study, TNBC MDA-MB-231 and Hs578T non-TNBC MCF-7 BT474 tumor-bearing mice were treated sunitinib, an drug, using a clinically relevant schedule. drug was administered one week then discontinued. Tumor growth invasion observed, patterns detected PAS/endomucin staining. Moreover, hypoxia VM-associated proteins evaluated Hypoxyprobe kits immunohistochemistry, respectively. Sunitinib significantly inhibited tumor However, tumors regrew more aggressive when treatment stopped. discontinuation had no significant effect on behavior vessels blocked by during which number channels increased resulted rebound after sunitinib discontinuation. VE-cadherin Twist1 upregulated sunitinib-treated Furthermore, significance upregulation validated 174 cancers. results from specimens indicated VM-positive cases than those cases. HIF-1α, MMP2, VE-cadherin, expressed higher level compared non-TNBC. aconclusion, promoted VM. status could be helpful to predict therapy patients TNBC.