Gene alterations in tumor-associated endothelial cells from endometrial cancer

Abstract

The alterations in the gene expression profile of tumor-associated human endometrial endothelial cells (HEECs) may allow opportunities for developing new therapeutic approaches to inhibit angiogenesis in endometrial cancer. The aim of this study was to identify the different gene expression pattern between tumor-associated HEECs and normal HEECs. To elucidate the molecular mechanisms governing the abnormal vasculature in endometrial cancer, we examined global expression patterns of purified endothelial cells from three endometrial cancers and three age-matched normal endometria using oligonucleotide microarrays. We also performed in vitro culture and identified the endothelial origin, as well as observing the functional characteristics in angiogenesis, of HEECs from the two different sources. Microarray analyses revealed distinct gene expression patterns and consistent up-regulation of certain endometrial endothelial marker genes across patient samples. More than 300 genes that exhibited > or =2-fold differences were identified in tumor-associated HEECs. Pathway analysis showed that pathways of Cell cycle, Cell adhesion molecules (CAMs), focal adhesion, and extracellular matrix (ECM)-receptor interaction were obviously predominant. The results of the microarray analysis were confirmed by quantitative real-time PCR, immunohistochemistry, and/or Western blotting. Moreover, although the tumor-associated HEECs did not show faster proliferation than normal HEECs, they exhibited enhanced migration ability, potent invasiveness, and elevated tube formation in vitro. The present study shows that tumor and normal endothelium differ at the molecular level, and additional characterization of this gene expression database will provide insights into the angiogenesis of endometrial cancers and might be of great benefit for finding potential therapeutic targets.