Effects of combretastatin A-4 phosphate on canine normal and tumor tissue-derived endothelial cells

Abstract Combretastatin A-4 phosphate (CA4P) selectively blocks tumor blood flow. However, the detailed mechanisms through which CA4P specifically affects tumor blood vessels are not well understood. Recent reports revealed that tumor tissue-derived endothelial cells (TECs) have various specific features in comparison with normal tissue-derived endothelial cells (NECs). Thus, abnormalities in TECs may be involved in the selective vascular blockade mechanism of CA4P. In this study, we evaluated the effects of CA4P on canine NECs and TECs using confocal microscopy. NECs exhibited different susceptibilities at subconfluence and at 100% confluence. In addition, inhibition of vascular endothelial cadherin (VE-cadherin) in NECs increased the sensitivity of the cells to CA4P. TECs seemed to be more susceptible to CA4P than NECs. The expression pattern of VE-cadherin in TECs was abnormal compared with that of NECs, suggesting that VE-cadherin may have functional abnormalities in these cells. Taken together, these results indicate that the tumor-vascular selectivity of CA4P may be related to VE-cadherin dysfunction in TECs.