Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan
Citations Over TimeTop 10% of 2016 papers
Abstract
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-κB 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.
Related Papers
- → Non-proteoglycan forms of biglycan increase with age in human articular cartilage(1993)139 cited
- → Distinct Secondary Structures of the Leucine-rich Repeat Proteoglycans Decorin and Biglycan(1999)38 cited
- Early elevation of transforming growth factor-beta, decorin, and biglycan mRNA levels during cartilage matrix restoration after mild proteoglycan depletion.(1997)
- → Aberrant Expressions of Decorin and Biglycan Genes in the Carbohydrate-Deficient Glycoprotein Syndrome1(1995)16 cited