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Serglycin Is Implicated in the Promotion of Aggressive Phenotype of Breast Cancer Cells

Författare

  • Angeliki Korpetinou
  • Spyros S. Skandalis
  • Aristidis Moustakas
  • Kaisa Happonen
  • Heidi Tveit
  • Kristian Prydz
  • Vassiliki T. Labropoulou
  • Efstathia Giannopoulou
  • Haralambos P. Kalofonos
  • Anna Blom
  • Nikos K. Karamanos
  • Achilleas D. Theocharis

Summary, in English

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 similar to 250 kDa and carrying chondroitin sulfate side chains, mainly composed of 4-sulfated (similar to 87%), 6-sulfated (similar to 10%) and non-sulfated (similar to 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.

Avdelning/ar

Publiceringsår

2013

Språk

Engelska

Publikation/Tidskrift/Serie

PLoS ONE

Volym

8

Issue

10

Dokumenttyp

Artikel i tidskrift

Förlag

Public Library of Science (PLoS)

Ämne

  • Other Basic Medicine
  • Medicinal Chemistry

Status

Published

Forskningsgrupp

  • Clinical Chemistry, Malmö
  • Protein Chemistry, Malmö

ISBN/ISSN/Övrigt

  • ISSN: 1932-6203