Breast cancer cells induce stromal fibroblasts to secrete ADAMTS1 for cancer invasion through an epigenetic change
Journal
PLoS ONE
Journal Volume
7
Journal Issue
4
Pages
e35128
Date Issued
2012
Author(s)
Tyan S.-W.
Hsu C.-H.
Peng K.-L.
Chen C.-C.
Lee E.Y.-H.P.
Shew J.-Y.
Juan L.-J.
Lee W.-H.
Abstract
Microenvironment plays an important role in cancer development. We have reported that the cancer-associated stromal cells exhibit phenotypic and functional changes compared to stromal cells neighboring to normal tissues. However, the molecular mechanisms as well as the maintenance of these changes remain elusive. Here we showed that through co-culture with breast cancer cells for at least three to four passages, breast normal tissue-associated fibroblasts (NAFs) gained persistent activity for promoting cancer cell invasion, partly via up-regulating ADAM metallopeptidase with thrombospondin type 1 motif, 1 (ADAMTS1). Furthermore, we demonstrated that the DNA methylation pattern in the ADAMTS1 promoter has no alteration. Instead, the loss of EZH2 binding to the ADAMTS1 promoter and the resulting decrease of promoter-associated histone H3K27 methylation may account for the up-regulation of ADAMTS1. Importantly, the lack of EZH2 binding and the H3K27 methylation on the ADAMTS1 promoter were sustained in cancer cell-precocultured NAFs after removal of cancer cells. These results suggest that cancer cells are capable of inducing stromal fibroblasts to secrete ADAMTS1 persistently for their invasion and the effect is epigenetically inheritable. ? 2012 Tyan et al.
SDGs
Other Subjects
ADAMTS1 protein; DNA; histone H3; transcription factor EZH2; ADAM protein; ADAMTS1 protein, human; proteoglycan; serglycin; vesicular transport protein; article; breast cancer; cancer cell; cancer cell culture; cancer invasion; cell invasion; coculture; controlled study; DNA methylation; epigenetics; fibroblast; histone methylation; human; human cell; promoter region; protein binding; protein expression; protein secretion; upregulation; cell culture; chromatin immunoprecipitation; enzyme linked immunosorbent assay; female; fibroblast; genetic epigenesis; genetics; immunoprecipitation; in vitro study; metabolism; metastasis; real time polymerase chain reaction; tumor cell line; Western blotting; ADAM Proteins; Blotting, Western; Cell Line, Tumor; Cells, Cultured; Chromatin Immunoprecipitation; Coculture Techniques; Enzyme-Linked Immunosorbent Assay; Epigenesis, Genetic; Female; Fibroblasts; Humans; Immunoprecipitation; Neoplasm Metastasis; Proteoglycans; Real-Time Polymerase Chain Reaction; Vesicular Transport Proteins
Type
journal article