Myofibroblast-derived SFRP1 as potential inhibitor of colorectal carcinoma field effect

PLoS One. 2014 Nov 18;9(11):e106143. doi: 10.1371/journal.pone.0106143. eCollection 2014.

Abstract

Epigenetic changes of stromal-epithelial interactions are of key importance in the regulation of colorectal carcinoma (CRC) cells and morphologically normal, but genetically and epigenetically altered epithelium in normal adjacent tumor (NAT) areas. Here we demonstrated retained protein expression of well-known Wnt inhibitor, secreted frizzled-related protein 1 (SFRP1) in stromal myofibroblasts and decreasing epithelial expression from NAT tissues towards the tumor. SFRP1 was unmethylated in laser microdissected myofibroblasts and partially hypermethylated in epithelial cells in these areas. In contrast, we found epigenetically silenced myofibroblast-derived SFRP1 in CRC stroma. Our results suggest that the myofibroblast-derived SFRP1 protein might be a paracrine inhibitor of epithelial proliferation in NAT areas and loss of this signal may support tumor proliferation in CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / metabolism*
  • Colorectal Neoplasms / metabolism*
  • DNA Methylation
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • HCT116 Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Myofibroblasts / metabolism*

Substances

  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • SFRP1 protein, human

Associated data

  • GEO/GSE37364
  • GEO/GSE4183

Grants and funding

This study was supported in part by the National Office for Research and Technology, Hungary, Grant number: TECH08-AI/2-2008_0114. Funder's website: www.magzrt.hu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no other funding to this study.