Altered expression of epithelial-to-mesenchymal transition proteins in extraprostatic prostate cancer.

Clare Verrill,Emma Morris,Chad Mckee,Michael White,Freddie Hamdy,Richard J Bryant,Lucia Cerundolo,Ruth Muschel,Christiana Kartsonaki,Indrika Ratnayaka,Simon Brewster,Eve Fryer,Hans Lilja,Luke Marsden,Xin Lu

doi:10.18632/oncotarget.6689

Abstract

Epithelial to mesenchymal transition (EMT) of cancer cells involves loss of epithelial polarity and adhesiveness, and gain of invasive and migratory mesenchymal behaviours. EMT occurs in prostate cancer (PCa) but it is unknown whether this is in specific areas of primary tumours. We examined whether any of eleven EMT-related proteins have altered expression or subcellular localisation within the extraprostatic extension component of locally advanced PCa compared with other localisations, and whether similar changes may occur in in vitro organotypic PCa cell cultures and in vivo PCa models. Expression profiles of three proteins (E-cadherin, Snail, and α-smooth muscle actin) were significantly different in extraprostatic extension PCa compared with intra-prostatic tumour, and 18/27 cases had an expression change of at least one of these three proteins. Of the three significantly altered EMT proteins in pT3 samples, one showed similar significantly altered expression patterns in in vitro organotypic culture models, and two in in vivo Pten-/- model samples. These results suggest that changes in EMT protein expression can be observed in the extraprostatic extension component of locally invasive PCa. The biology of some of these changes in protein expression may be studied in certain in vitro and in vivo PCa models.

Highlights

It is estimated that 220,800 men in the United States will be diagnosed with prostate cancer (PCa) during 2015 and 27,540 men will die from this malignancy [1], usually from metastatic disease
In light of the increasing research interest in the process of Epithelial to mesenchymal transition (EMT) as a mechanism of PCa progression, we investigated whether in vitro and in vivo PCa models commonly used in the laboratory to investigate mechanisms of PCa cellular invasion such as EMT demonstrate any similar changes to those observed in human pT3a radical prostatectomy (RP) specimens
Significant expression changes of α-smooth muscle actin, E-cadherin and Snail were observed in tumours in Pten-/- mice (n = 7) compared with benign Pten+/+ mice (n = 6) (Figure 6). These results suggest EMT occurs in extraprostatic extension components of locally advanced PCa

Summary

Introduction

It is estimated that 220,800 men in the United States will be diagnosed with prostate cancer (PCa) during 2015 and 27,540 men will die from this malignancy [1], usually from metastatic disease. Within the TNM classification of PCa, the pT3a stage of this malignancy describes extraprostatic extension of the tumour beyond the prostatic capsule. Extraprostatic extension of PCa is associated with recurrence and metastasis following radical treatment [2,3,4,5]. EMT occurs in several cancers including PCa [12,13,14,15,16,17,18] and can predict recurrence after RP [19, 20], but it is unknown whether it occurs in specific areas of primary PCa such as extraprostatic extension in pT3a tumours. We investigated potential differences in EMT protein expression between the extraprostatic extension and intraprostatic tumour components of pT3a PCa in RP specimens. In light of the increasing research interest in the process of EMT as a mechanism of PCa progression, we investigated whether in vitro and in vivo PCa models commonly used in the laboratory to investigate mechanisms of PCa cellular invasion such as EMT demonstrate any similar changes to those observed in human pT3a RP specimens

Methods

Results

Conclusion