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A role for STEAP2 in prostate cancer progression

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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.

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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

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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.

Author information

Authors and Affiliations

  1. Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea, SA2 8PP, Wales, UK

    Helen Whiteland, Claire Morgan, Paul Lewis, Spencer Jenkins & Shareen H. Doak

  2. Department of Cellular Pathology, Singleton Hospital, Abertawe Bro Morgannwg University NHS Trust, Swansea, SA2 8QA, Wales, UK

    Samantha Spencer-Harty & David Hywel Thomas

  3. Department of Surgery, Cardiff School of Medicine, Heath Park, Cardiff, CF14 4XW, Wales, UK

    Howard Kynaston & Spencer Jenkins

  4. Department of Urology, Morriston Hospital, Abertawe Bro Morgannwg University NHS Trust, Swansea, SA6 6NL, Wales, UK

    Pradeep Bose & Neil Fenn

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  1. Helen Whiteland
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Corresponding author

Correspondence to Shareen H. Doak.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10585_2014_9679_MOESM1_ESM.doc

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

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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Whiteland, H., Spencer-Harty, S., Morgan, C. et al. A role for STEAP2 in prostate cancer progression. Clin Exp Metastasis 31, 909–920 (2014). https://doi.org/10.1007/s10585-014-9679-9

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  • DOI: https://doi.org/10.1007/s10585-014-9679-9

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