RRC ID 68874
Author Maishi N, Ohba Y, Akiyama K, Ohga N, Hamada J, Nagao-Kitamoto H, Alam MT, Yamamoto K, Kawamoto T, Inoue N, Taketomi A, Shindoh M, Hida Y, Hida K.
Title Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan.
Journal Sci Rep
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.
Volume 6
Pages 28039
Published 2016-6-13
DOI 10.1038/srep28039
PII srep28039
PMID 27295191
PMC PMC4904795
MeSH Animals Biglycan / genetics* Biglycan / metabolism Cell Line, Tumor DNA Methylation* Endothelial Cells / cytology Endothelial Cells / metabolism Endothelial Cells / pathology* Endothelial Cells / transplantation* Epigenesis, Genetic Female Gene Expression Regulation, Neoplastic Humans Lung Neoplasms / genetics Lung Neoplasms / metabolism Lung Neoplasms / pathology Lung Neoplasms / secondary* MAP Kinase Signaling System Melanoma / genetics Melanoma / metabolism Melanoma / pathology* Mice NF-kappa B / metabolism NIH 3T3 Cells Neoplasm Metastasis Neoplasm Transplantation RAW 264.7 Cells Up-Regulation
IF 3.998
DNA material CSII-CMV-MCS (RDB04377) CS-RfA-CMV-mRFP1 (RDB05747) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)