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Role of the EpCAM (CD326) in prostate cancer metastasis and progression

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Abstract

Despite significant advances in surgery, radiotherapy and chemotherapy to treat prostate cancer (CaP), many patients die of secondary disease (metastases). Current therapeutic approaches are limited, and there is no cure for metastatic castration-resistant prostate cancer (CRPC). Epithelial cell adhesion molecule (EpCAM, also known as CD326) is a transmembrane glycoprotein that is highly expressed in rapidly proliferating carcinomas and plays an important role in the prevention of cell–cell adhesion, cell signalling, migration, proliferation and differentiation. Stably and highly expressed EpCAM has been found in primary CaP tissues, effusions and CaP metastases, making it an ideal candidate of tumour-associated antigen to detect metastasis of CaP cells in the circulation as well as a promising therapeutic target to control metastatic CRPC disease. In this review, we discuss the implications of the newly identified roles of EpCAM in terms of its diagnostic and metastatic relevance to CaP. We also summarize EpCAM expression in human CaP and EpCAM-mediated signalling pathways in cancer metastasis. Finally, emerging and innovative approaches to the management of the disease and expanding potential therapeutic applications of EpCAM for targeted strategies in future CaP therapy will be explored.

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Abbreviations

ADCC:

Antibody-dependent cellular cytotoxicity

Adv:

Adenovirus

AR:

Androgen receptor

BPH:

Benign prostate hyperplasia

bsAb:

Bispecific antibody

CaP:

Prostate cancer

CAS:

Cancer-associated stroma

CD326:

Epithelial cell adhesion molecule

CDC:

Complement-dependent cytotoxicity

CPTCs:

Circulating prostate tumour cells

CRPC:

Castration-resistant prostate cancer

CSCs:

Cancer stem cells

CTCs:

Circulating tumour cells

DARPin:

Designed ankyrin repeat protein

DTX:

Docetaxel

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

EpCAM:

Epithelial cell adhesion molecule

EpEx:

EpCAM Extracellular domain

EpICD:

EpCAM Intracellular domain

EPR:

Enhanced permeability and retention

FcγR:

Fcγ Receptors

FDA:

Food and drug administration

GFP:

Green fluorescent protein

HGPIN:

High-grade prostatic intraepithelial neoplasias

i.p.:

Intraperitoneal

IHC:

Immunohistochemistry

MAbs:

Monoclonal antibodies

MDR:

Minimum residual disease

NOD/SCID:

Non-obese diabetic/severe combined immunodeficient

PSA:

Prostate-specific antigen

RIP:

Regulated intramembrane proteolysis

RP:

Radical prostatectomy

SCID:

Severe combined immunodeficient

siRNA:

Short interfering RNA

TAAs:

Tumour-associated antigens

TMA:

Tissue microarrays

TY:

Thyroglobulin

VEGF:

Vascular endothelial growth factor

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Acknowledgments

This work was supported in part by a NHMRC Career Development Fellowship (YL), Surgical & Urological Research Found (SURF) (PJC) from Urology Sydney and Cancer Research Trust Fund at Cancer Care Centre, St George Hospital (PHG and KHJ). The authors thank Professor Pamela Russell (Oncology Research Centre, Sydney) who kindly provided prostate cancer cell lines and Professor Warick Delprado (Douglass Hanly Moir Pathology, Sydney) who kindly provided prostate cancer specimens. The authors also thank Ms Jingli Hao and Ms Julia Beretov (Cancer Care Centre, St George Hospital) for their excellent technical assistance.

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Authors and Affiliations

  1. Cancer Care Centre, St. George Hospital, Gray St Kogarah, Sydney, NSW, 2217, Australia

    Jie Ni, Peter H. Graham, Kearsley H. John & Yong Li

  2. St George Clinical School, Faculty of Medicine, University of New South Wales, Kensington, NSW, 2052, Australia

    Jie Ni, Paul J. Cozzi, Peter H. Graham, Kearsley H. John & Yong Li

  3. Department of Surgery, St. George Hospital, Sydney, NSW, 2217, Australia

    Paul J. Cozzi

  4. School of Medicine, Deakin University, Waurn Ponds, Victoria, 3217, Australia

    Wei Duan & Sarah Shigdar

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  1. Jie Ni
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  2. Paul J. Cozzi
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Correspondence to Paul J. Cozzi or Yong Li.

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Ni, J., Cozzi, P.J., Duan, W. et al. Role of the EpCAM (CD326) in prostate cancer metastasis and progression. Cancer Metastasis Rev 31, 779–791 (2012). https://doi.org/10.1007/s10555-012-9389-1

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