Epithelial cell adhesion molecule (EpCAM) is involved in prostate cancer chemotherapy/radiotherapy response in vivo

Jie Ni,Julia Beretov,Yong Li,Wei Duan,Paul Cozzi,Peter Graham,Joseph Bucci

doi:10.1186/s12885-018-5010-5

Jie Ni, Julia Beretov + Show 5 more

Open Access

https://doi.org/10.1186/s12885-018-5010-5

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Abstract

BackgroundDevelopment of chemo−/radioresistance is a major challenge for the current prostate cancer (CaP) therapy. We have previously demonstrated that epithelial cell adhesion molecule (EpCAM) is associated with CaP growth and therapeutic resistance in vitro, however, the role of EpCAM in CaP in vivo is not fully elucidated. Here, we aimed to investigate how expression of EpCAM is involved in CaP growth and chemo−/radiotherapy response in NOD/SCID mouse models in vivo and to validate its role as a therapeutic target for CaP therapy.MethodsEpCAM was knocked down in PC-3 CaP cell line using short hairpin RNA (shRNA). The effect of EpCAM-knockdown (KD) on tumour growth, chemo−/radiotherapy response and animal survival was evaluated on subcutaneous (s.c) and orthotopic mouse models.ResultsWe found that KD of EpCAM significantly inhibited tumour growth, increased xenograft sensitivity to chemotherapy/radiotherapy, and prolonged the survival of tumour-bearing mice. In addition, we demonstrated that KD of EpCAM is associated with downregulation of the PI3K/Akt/mTOR pathway.ConclusionsIn conclusion, our data confirms that CaP growth and chemo−/radioresistance in vivo is associated with over-expression of EpCAM, which serves both a functional biomarker and promising therapeutic target.

Highlights

Development of chemo−/radioresistance is a major challenge for the current prostate cancer (CaP) therapy
We demonstrate for the first time that epithelial cell adhesion molecule (EpCAM) is involved in tumour growth, chemo−/radiotherapy response and associated with activation of the PI3K/Akt/mTOR signalling pathway in Prostate cancer (CaP) animal models in vivo
Western blot (Fig. 1a) and IF staining (Fig. 1b) and Quantitative real-time PCR (qRT-PCR) (Fig. 1c) showed that EpCAM expression level was markedly reduced in PC-3-EpCAM-KD cells compared with PC-3-EpCAM-scr and PC-3 cell lines

Summary

Introduction

Development of chemo−/radioresistance is a major challenge for the current prostate cancer (CaP) therapy. We have previously demonstrated that epithelial cell adhesion molecule (EpCAM) is associated with CaP growth and therapeutic resistance in vitro, the role of EpCAM in CaP in vivo is not fully elucidated. We aimed to investigate how expression of EpCAM is involved in CaP growth and chemo−/radiotherapy response in NOD/SCID mouse models in vivo and to validate its role as a therapeutic target for CaP therapy. For recurrent and metastatic diseases, while initially responsive to androgen deprivation therapy, recurrent castration-resistant prostate cancer (CRPC) will inevitably occur, and is often associated with a poor prognosis. Despite the revolutionary targeted therapies and immunotherapy in CaP management, chemotherapy retains a key role in the treatment of advanced CaP disease.

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