Abstract
Tumor blood vessels play an important role in tumor progression and metastasis. Thus, targeting the tumor blood vessels is an important strategy in cancer therapy. Tumor blood vessels generally arise from pre-existing vessels and have been thought to be genetically normal. However, they have been shown to differ from their normal counterparts e.g., with regard to morphological changes. We isolated tumor endothelial cells (TECs) from mouse tumor xenografts and showed that they were abnormal. TECs up-regulate many genes, proliferate more rapidly, and migrate more than normal endothelial cells (NECs). Furthermore, the TECs in our study were cytogenetically abnormal. TECs were drug resistant to paclitaxel with upregulation of multidrug resistance 1 (MDR1) mRNA, compared to NECs. Tumor-conditioned medium treatment caused drug resistance in NEC. We concluded that TECs can acquire cytogenetic abnormalities while in the tumor microenvironment.
In order to develop ideal antiangiogenic therapies, it is important to understand the crosstalk between blood vessels and the tumor microenvironment.
This review considers the current studies on TEC abnormalities, and discusses the possible mechanism by which the tumor microenvironment produces abnormal TECs.
