Tumor blood vessels play an important role in tumor progression and metastasis. Thus, targeting tumor blood vessels is an important strategy for cancer therapy, especially for head and neck cancer patients. Tumor blood vessels generally sprout from pre-existing vessels and have been thought to be genetically normal. However, tumor blood vessels have been shown to differ from their normal counterparts, for example, by changes in morphology. The authors isolated tumor endothelial cells (TECs) from mouse tumor xenografts and have shown that the TECs are abnormal. TECs up-regulate many genes and proliferate more rapidly and migrate more than normal endothelial cells (NECs). Furthermore, TECs were found to be cytogenetically abnormal. We conclude that TECs can acquire cytogenetic abnormalities while in a tumor microenvironment.To develop ideal antiangiogenic therapies, understanding the crosstalk between blood vessels and the tumor microenvironment is important.Here, we provide an overview of the current studies on TEC abnormalities and a discussion about possible mechanisms for how tumor the microenvironment makes TECs abnormal.

Multiple gene disorders have been shown to be involved in carcinogenesis. Mutation, translocation and amplification have been identified in so-called oncogenes, and inactivation of antioncogenes by mutation and deletion has been shown. E1AF is an ets-oncogene family transcription factor, and has been shown to upregulate multiple matrix metalloproteinase (MMP) genes that contribute to the malignant phenotype of cancer cells by inducing invasive and metastatic activities. EWS/ETS fusions are frequently observed in Ewing's sarcoma, and we have revealed that EWS/ETS chimeric protein activates telomerase activity by upregulating human telomerase reverse transcriptase (hTERT), but the transcriptional activation of hTERT by EWS/ETS was indirect, and EWS/ETS was seen to function as a co-activator for TERT transcription. A number of oncogenes and cancer-related genes contain AU-rich element (ARE) in non-coding regions of transcribed mRNA. HuR is a RNA-binding protein that has the potential to stabilize ARE-containing mRNAs. HuR is known to shuttle between the nucleus and the cytoplasm via several export pathways. When normal cells are exposed to stress, HuR is exported to the cytoplasm in a chromosome maintenance region 1 (CRM1)-dependent manner. However, we demonstrate that HuR is CRM-1 independently exported to the cytoplasm in oral cancer cells. ARE-mRNAs were also exported to the cytoplasm and stabilized in the oral cancer cells, which were inhibited by HuR knockdown. These findings suggest that transcriptional and translational abnormalities of oncogenes may contribute to the carcinogenesis of oral epithelial cells.