Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan

Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-kappa B and extracellular signal-regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis

NMR Spectroscopic Study of the Complexation Behaviors of Deuterated Cyclodextrins and [60]Fullerene

Cyclodextrins (CDxs) have been selectively deuterated using a Ru/C-catalyzed H–D exchange reaction in D₂O. The structures of the deuterated CDxs barely changed and their ¹H NMR spectra became very simple, which made it possible for the deuterated CDxs to be applied to the analysis of CDx complexes. Furthermore, the deuterated CDxs allowed for the existence of the equilibrium between free and complexed CDx to be confirmed, even at rt

Enhancement of in vitro cell motility and invasiveness of human malignant pleural mesothelioma cells through the HIF-1 alpha-MUC1 pathway

In this study, we examined the effects of hypoxia on the malignancy of human malignant pleural mesothelioma (MPM) cell lines, and found (I) hypoxia enhanced motility and invasiveness of human malignant pleural mesothelioma (MPM) cells; (2) this phenomenon resulted from increased expression of sialylated MUC1 through the activation of HIF-1 pathway; (3) two HIF-binding sites located in the promoter region of MUC1 were important for MUC1 transactivation under hypoxia. These findings are useful for better understanding molecular mechanisms of aggressive behavior of MPM cells and for targeting them in the clinical therapies for MPM patients