Heparan sulfate proteoglycans and human breast cancer epithelial cell tumorigenicity

Rachel K. Okolicsanyi, Andre J. Van Wijnen, Simon M. Cool, Gary S. Stein, Lyn R. Griffiths, Larisa M. Haupt

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Heparan sulfate proteoglycans (HSPGs) are key components of the extracellular matrix that mediate cell proliferation, invasion, and cellular signaling. The biological functions of HSPGs are linked to their co-stimulatory effects on extracellular ligands (e.g., WNTs) and the resulting activation of transcription factors that control mammalian development but also associated with tumorigenesis. We examined the expression profile of HSPG core protein syndecans (SDC1-4) and glypicans (GPC1-6) along with the enzymes that initiate or modify their glycosaminoglycan chains in human breast cancer (HBC) epithelial cells. Gene expression in relation to cell proliferation was examined in the HBC cell lines MCF-7 and MDA-MB-231 following treatment with the HS agonist heparin. Heparin increased gene expression of chain initiation and modification enzymes including EXT1 and NDST1, as well as core proteins SDC2 and GPC6. With HS/Wnt interactions established, we next investigated WNT pathway components and observed that increased proliferation of the more invasive MDA-MB-231 cells is associated with activation of the Wnt signaling pathway. Specifically, there was substantial upregulation (>5-fold) of AXIN1, WNT4A, and MYC in MDA-MB-231 but not in MCF-7 cells. The changes in gene expression observed for HSPG core proteins and related enzymes along with the associated Wnt signaling components suggest coordinated interactions. The influence of HSPGs on cellular proliferation and invasive potential of breast cancer epithelial cells are cell and niche specific. Further studies on the interactions between HSPGs and WNT ligands may yield clinically relevant molecular targets, as well as new biomarkers for characterization of breast cancer progression.

Original languageEnglish (US)
Pages (from-to)967-976
Number of pages10
JournalJournal of cellular biochemistry
Volume115
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • BREAST CANCER
  • GENE EXPRESSION
  • HEPARAN SULFATE PROTEOGLYCANS
  • MCF-7
  • MDA-MB-231
  • Wnt SIGNALING

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Okolicsanyi, R. K., Van Wijnen, A. J., Cool, S. M., Stein, G. S., Griffiths, L. R., & Haupt, L. M. (2014). Heparan sulfate proteoglycans and human breast cancer epithelial cell tumorigenicity. Journal of cellular biochemistry, 115(5), 967-976. https://doi.org/10.1002/jcb.24746