Tumour Endothelial Cells in High Metastatic Tumours Promote Metastasis Via Epigenetic Dysregulation of Biglycan

Overview

Journal Sci Rep

Specialty Science

Date 2016 Jun 14

PMID 27295191

Citations 68

Authors

Nako Maishi

Yusuke Ohba

Kosuke Akiyama

Noritaka Ohga

Jun-Ichi Hamada

Hiroko Nagao-Kitamoto

Mohammad Towfik Alam

Kazuyuki Yamamoto

Taisuke Kawamoto

Nobuo Inoue

Akinobu Taketomi

Masanobu Shindoh

Yasuhiro Hida

Kyoko Hida

Affiliations

Soon will be listed here.

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.

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