Serglycin is implicated in the promotion of aggressive phenotype of breast cancer cells

PLoS One. 2013 Oct 31;8(10):e78157. doi: 10.1371/journal.pone.0078157. eCollection 2013.


Serglycin is a proteoglycan expressed by some malignant cells. It promotes metastasis and protects some tumor cells from complement system attack. In the present study, we show for the first time the in situ expression of serglycin by breast cancer cells by immunohistochemistry in patients' material. Moreover, we demonstrate high expression and constitutive secretion of serglycin in the aggressive MDA-MB-231 breast cancer cell line. Serglycin exhibited a strong cytoplasmic staining in these cells, observable at the cell periphery in a thread of filaments near the cell membrane, but also in filopodia-like structures. Serglycin was purified from conditioned medium of MDA-MB-231 cells, and represented the major proteoglycan secreted by these cells, having a molecular size of ~ 250 kDa and carrying chondroitin sulfate side chains, mainly composed of 4-sulfated (~ 87%), 6-sulfated (~ 10%) and non-sulfated (~ 3%) disaccharides. Purified serglycin inhibited early steps of both the classical and the lectin pathways of complement by binding to C1q and mannose-binding lectin. Stable expression of serglycin in less aggressive MCF-7 breast cancer cells induced their proliferation, anchorage-independent growth, migration and invasion. Interestingly, over-expression of serglycin lacking the glycosaminoglycan attachment sites failed to promote these cellular functions, suggesting that glycanation of serglycin is a pre-requisite for its oncogenic properties. Our findings suggest that serglycin promotes a more aggressive cancer cell phenotype and may protect breast cancer cells from complement attack supporting their survival and expansion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cell Proliferation
  • Female
  • Humans
  • MCF-7 Cells
  • Mannose-Binding Lectin / metabolism
  • Protein Binding
  • Proteoglycans / metabolism*
  • Vesicular Transport Proteins / metabolism*


  • Mannose-Binding Lectin
  • Proteoglycans
  • Vesicular Transport Proteins
  • serglycin

Grants and funding

This research has been co-financed by the European Union (European Social Fund – ESF) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF) - Research Funding Program: Heracleitus II. Investing in knowledge society through the European Social Fund. This work was also supported in part by grants from Mizutani Foundation for Glycosciences (ADT), Swedish Research Foundation (K2012-66X-14928-09-5) and Cancerfonden (AMB, KEH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.