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Clinical & Experimental Metastasis

, Volume 31, Issue 8, pp 909–920 | Cite as

A role for STEAP2 in prostate cancer progression

  • Helen Whiteland
  • Samantha Spencer-Harty
  • Claire Morgan
  • Howard Kynaston
  • David Hywel Thomas
  • Pradeep Bose
  • Neil Fenn
  • Paul Lewis
  • Spencer Jenkins
  • Shareen H. DoakEmail author
Research Paper

Abstract

Prostate adenocarcinoma is the second most frequent cancer worldwide and is one of the leading causes of male cancer-related deaths. However, it varies greatly in its behaviour, from indolent non-progressive disease to metastatic cancers with high associated mortality. The aim of this study was to identify predictive biomarkers for patients with localised prostate tumours most likely to progress to aggressive disease, to facilitate future tailored clinical treatment and identify novel therapeutic targets. The expression of 602 genes was profiled using oligoarrays, across three prostate cancer cell lines: CA-HPV-10, LNCaP and PC3, qualitatively identifying several potential prognostic biomarkers. Of particular interest was six transmembrane epithelial antigen of the prostate (STEAP) 1 and STEAP 2 which was subsequently analysed further in prostate cancer tissue samples following optimisation of an RNA extraction method from laser captured cells isolated from formalin-fixed paraffin-embedded biopsy samples. Quantitative analysis of STEAP1 and 2 gene expression were statistically significantly associated with the metastatic cell lines DU145 and PC3 as compared to the normal prostate epithelial cell line, PNT2. This expression pattern was also mirrored at the protein level in the cells. Furthermore, STEAP2 up-regulation was observed within a small patient cohort and was associated with those that had locally advanced disease. Subsequent mechanistic studies in the PNT2 cell line demonstrated that an over-expression of STEAP2 resulted in these normal prostate cells gaining an ability to migrate and invade, suggesting that STEAP2 expression may be a crucial molecule in driving the invasive ability of prostate cancer cells.

Keywords

Prostate cancer STEAP1 STEAP2 Carcinogenesis Metastasis Migration Invasion 

Abbreviations

BMP

Bone morphogenic protein

DISC

Death inducing signalling complex

ECM

Extracellular matrix

ERK

Extracellular signal-regulated kinases

FFPE

Formalin fixed paraffin embedded

H&E

Haematoxylin and eosin

HRL

High risk localised

LCM

Laser capture microdissection

LRL

Low risk localised

BPH

Matrix metalloproteinase

MMP

Benign prostate hyperplasia

MAPK

Mitogen activated protein kinase

PCa

Prostate cancer

PSA

Prostate specific antigen

TIMP

Tissue inhibitor metalloproteinase

TGF

Transforming growth factor

TRUS

Transrectal ultrasound

STEAP

Six transmembrane epithelial antigen of the prostate

Notes

Acknowledgments

Funding for this work was kindly provided by grants to SHD from the National Institute for Social Care and Health Research (NISCHR) and the Swansea Prostate Cancer Research Fund.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10585_2014_9679_MOESM1_ESM.doc (92 kb)
Supplemental Fig. 1: List of all genes screened in the oligoarray analysis. A comprehensive list of genes analysed in the oligoarray analysis displayed based on the signalling pathway array type they were positioned upon. Supplementary material 1 (DOC 91 kb)
10585_2014_9679_MOESM2_ESM.doc (72 kb)
Supplemental Fig. 2: Oligoarray gene spot intensities for all four cell lines. Using oligoarrays tailored to four various pathways: WNT signalling pathway, TGFβ/BMP signalling pathway, ECM and adhesion molecules, and PCa biomarkers; over 600 genes were analysed for qualitative identification of potential biomarkers of aggressive PCa. Supplementary material 2 (DOC 72 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Helen Whiteland
    • 1
  • Samantha Spencer-Harty
    • 2
  • Claire Morgan
    • 1
  • Howard Kynaston
    • 3
  • David Hywel Thomas
    • 2
  • Pradeep Bose
    • 4
  • Neil Fenn
    • 4
  • Paul Lewis
    • 1
  • Spencer Jenkins
    • 1
    • 3
  • Shareen H. Doak
    • 1
    Email author
  1. 1.Institute of Life Science, College of MedicineSwansea UniversitySwanseaWales, UK
  2. 2.Department of Cellular Pathology, Singleton HospitalAbertawe Bro Morgannwg University NHS TrustSwanseaWales, UK
  3. 3.Department of SurgeryCardiff School of MedicineCardiffWales, UK
  4. 4.Department of Urology, Morriston HospitalAbertawe Bro Morgannwg University NHS TrustSwanseaWales, UK

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