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Tumor Biology

, Volume 35, Issue 4, pp 3237–3245 | Cite as

d-glucuronyl C5-epimerase cell type specifically affects angiogenesis pathway in different prostate cancer cells

  • Eugenia E. Rosenberg
  • Tatiana Y. Prudnikova
  • Eugene R. Zabarovsky
  • Vladimir I. Kashuba
  • Elvira V. Grigorieva
Research Article

Abstract

d-glucuronyl C5-epimerase (GLCE) is involved in breast and lung carcinogenesis as a potential tumor suppressor gene, acting through inhibition of tumor angiogenesis and invasion/metastasis pathways. However, in prostate tumors, increased GLCE expression is associated with advanced disease, suggesting versatile effects of GLCE in different cancers. To investigate further the potential cancer-promoting effect of GLCE in prostate cancer, GLCE was ectopically re-expressed in morphologically different LNCaP and PC3 prostate cancer cells. Transcriptional profiles of normal PNT2 prostate cells, LNCaP, PC3 and DU145 prostate cancer cells, and GLCE-expressing LNCaP and PC3 cells were determined. Comparative analysis revealed the genes whose expression was changed in prostate cancer cells compared with normal PNT2 cells, and those differently expressed between the cancer cell lines (ACTA2, IL6, SERPINE1, TAGLN, SEMA3A, and CDH2). GLCE re-expression influenced mainly angiogenesis-involved genes (ANGPT1, SERPINE1, IGF1, PDGFB, TNF, IL8, TEK, IFNA1, and IFNB1) but in a cell type-specific manner (from basic deregulation of angiogenesis in LNCaP cells to significant activation in PC3 cells). Invasion/metastasis pathway was also affected (MMP1, MMP2, MMP9, S100A4, ITGA1, ITGB3, ERBB2, and FAS). The obtained results suggest activation of angiogenesis as a main molecular mechanism of pro-oncogenic effect of GLCE in prostate cancer. GLCE up-regulation plus expression pattern of a panel of six genes, discriminating morphologically different prostate cancer cell sub-types, is suggested as a potential marker of aggressive prostate cancer.

Keywords

d-glucuronyl C5-epimerase Heparan sulfate proteoglycan Prostate cancer Intratumor heterogeneity Transcriptional profiling Molecular marker 

Abbreviations

GLCE

d-glucuronyl C5-epimerase

HSPG

Heparan sulfate proteoglycan

Notes

Acknowledgments

The work was supported by the research grants from Russian Foundation for Basic Research (RFBR 12-04-01657_a), Ukranian State Foundation of Fundamental Research (F40/146-2011, F46/457-2011), UICC International Cancer Technology Transfer Fellowships (EVG, ICR/08/086; TYP, ICR/09/069), and FEBS Short-Term Fellowships (TYP). Authors thank Dr. Lyudmila Mostovich for technical assistance with the cell clone characterization.

Conflicts of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Eugenia E. Rosenberg
    • 1
  • Tatiana Y. Prudnikova
    • 2
  • Eugene R. Zabarovsky
    • 3
  • Vladimir I. Kashuba
    • 1
  • Elvira V. Grigorieva
    • 2
    • 3
  1. 1.Institute of Molecular Biology and GeneticsKiev 03143Ukraine
  2. 2.Institute of Molecular Biology and Biophysics SD RAMSNovosibirskRussia
  3. 3.MTCKarolinska InstituteStockholmSweden

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