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

• Maishi, Nako

• Ohba, Yusuke

• Akiyama, Kosuke

• Ohga, Noritaka

• Hamada, Jun-ichi

• Nagao-Kitamoto, Hiroko

• Alam, Mohammad Towfik

• Yamamoto, Kazuyuki

• Kawamoto, Taisuke

• Inoue, Nobuo

• Taketomi, Akinobu

• Shindoh, Masanobu

• Hida, Yasuhiro

• Hida, Kyoko

抄録

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.

収録刊行物

• Scientific reports

  Scientific reports 6 28039-, 2016-06-13

  Nature Publishing Group

キーワード

• Multidisciplinary

詳細情報

• CRID: 1050001339020565248
• NII論文ID: 120005819304
• DOI: 10.1038/srep28039
• HANDLE: 2115/62446
• ISSN: 20452322
• Web Site: https://www.nature.com/articles/srep28039
• Web Site: https://www.nature.com/articles/srep28039.pdf
• 本文言語コード: en
• 資料種別: journal article
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