The Effect of Aquaporin 1-Inhibition on Vasculogenic Mimicry in Malignant Mesothelioma

摘要: Malignant mesothelioma (MM) is an aggressive malignancy of the serosal membranes, with poor overall survival and quality life. Limited targeted treatment strategies exist due to restricted knowledge pathogenic pathways. Vasculogenic mimicry (VM) a newly described phenomenon associated increased aggressiveness in other malignancies, has been characterized MM. Normal mesothelium expresses aquaporin 1 (AQP1) retained expression improved AQP1 expressed by normal vascular endothelium involved mediating MM cell motility proliferation. We investigated role VM, its interaction pro-angiogenic factor endothelial growth A (VEGFA), which variably Matrigel VM assays were performed using NCI-H226 NCI-H28 lines primary cells hypoxia normoxia. The synthetic blocker AqB050 siRNA used inhibit AQP1, bevacizumab was VEGF. Inhibition resulted VEGFA secretion reduced but not No change seen cells. Combined inhibition VEGF had no effect on In heterotopic xenograft mouse model, did alter vessel formation. may interact play especially under hypoxic conditions, heterogeneity result different dominant pathways between patients.