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Cancer and Metastasis Reviews

, Volume 32, Issue 3–4, pp 535–551 | Cite as

The role of tumour-associated MUC1 in epithelial ovarian cancer metastasis and progression

  • Junli Deng
  • Li Wang
  • Hongmin Chen
  • Lei Li
  • Yiming Ma
  • Jie Ni
  • Yong Li
NON-THEMATIC REVIEW

Abstract

The most common ovarian cancer is epithelial ovarian cancer (EOC) characterised by few early symptoms, widespread peritoneal dissemination and ascites at advanced stages that result in poor prognosis. Despite the recent progress in its management, including surgery and chemotherapy, EOC remains the most lethal gynaecological malignancy in women. Due to the limitations of current therapeutic approaches, many patients die of secondary disease (metastasis). MUC1 is associated with cellular transformation and tumorigenicity and is considered as an attractive therapeutic target for cancer therapy owning to its over-expression in most adenocarcinomas including EOC. Tumour-associated MUC1 plays an important role in EOC metastasis and progression. In neoplastic tissues, MUC1 is underglycosylated and reveals epitopes that are masked in the normal cells. This feature makes it possible to target tumour-associated MUC1 with antibodies, toxins or radionuclides or use a vaccine targeting tumour-associated MUC1 antigen. The shed tumour-associated MUC1 in blood can be used as a diagnostic biomarker for EOC detection and monitoring. Our recent results have shown that over-expression of MUC1 plays a very important role in EOC progression and MUC1 is an ideal target for targeted therapy to control metastatic and recurrent EOC. This review will summarize some important new findings supporting the role of MUC1 in EOC metastasis and progression and focus on the MUC1-based targeted therapy for control of metastatic and recurrent EOC.

Keywords

MUC1 Epithelial ovarian cancer Tumour-associated antigen Metastasis Targeted cancer therapy 

Abbreviations

AC

α-conjugate

AR

Androgen receptor

CCR

Complete clinical remission

CSC

Cancer stem cell

CT

Cytoplasm tail

CTL

Cytotoxic T lymphocytes

DCs

Dendritic cells

DTX

Docetaxel

EGFR

Epidermal growth factor receptor

EIA

Enzyme-linked immunoassay

ELISA

Enzyme-linked immunosorbent assay

EMT

Epithelial–mesenchymal transition

EOC

Epithelial ovarian cancer

EPR

Enhanced permeability and retention

ER

Endoplasmic reticulum

ERKs

Extracellular signal-regulated kinases

HAMA

Human antimouse antibody

HMFG

Human milk fat globule

ICAM-1

Intercellular adhesion molecule-1

i.p.

Intraperitoneal

LET

Linear energy transfer

MAb

Monoclonal antibody

MAPK

Mitogen-activated protein kinase

MRD

Minimal residual disease

MUC1

Mucin 1

MUC1-C

MUC1 C-terminal subunit

MUC16

CA125

NK

Natural killer

ORα

Oestrogen receptor α

OS

Overall survival

OSE

Ovarian surface epithelium

PMIP

Protein MUC1 inhibitory peptide

QD-MUC1-DOX

Quantum dot-mucin1 aptamer-doxorubicin

RIT

Radioimmunotherapy

RTKs

Receptor tyrosine kinases

SIGLECS

Sialic acid-binding immunoglobulin superfamily lectins

SMART

Study of MAb Radioimmunotherapy

TAAs

Tumour-associated antigens

Tg

Transgenic

TM

Trans-membrane

TRs

Tandem repeats

VNTR

Variable number of tandem repeats

Notes

Acknowledgments

Our EOC projects were supported in part by an International Collaborative Grant from Henan Health Board, China and a National Health & Medical Research Council (NH&MRC) Career Development Fellowship (YL), Australia. The authors thank Associate Professor Peter Graham and Professor John Kearsley (Cancer Care Centre, St George Hospital, Sydney) for their ongoing support and Dr Jingli Hao and Ms Julia Beretov (Cancer Care Centre, St George Hospital, Sydney) for their excellent technical assistance.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Gynecologic Oncology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouChina
  2. 2.Cancer Care CentreSt George HospitalSydneyAustralia
  3. 3.Faculty of MedicineUniversity of New South WalesKensingtonAustralia

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