Annexin A3 is a mammary marker and a potential neoplastic breast cell therapeutic target

// Bashar Zeidan 1 , Thomas R. Jackson 2, 5 , Samantha E.T. Larkin 1 , Ramsey I. Cutress 1 , Gary R. Coulton 3 , Margaret Ashton-Key 1 , Nick Murray 1 , Graham Packham 1 , Vassilis Gorgoulis 2, 4, 5 , Spiros D. Garbis 1 , Paul A. Townsend 1, 2, 5 1 Cancer Sciences Unit, University of Southampton, Southampton, UK 2 Faculty Institute for Cancer Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK 3 St George’s Medical Biomics Centre, St. George’s University of London, London, UK 4 Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece 5 Manchester Centre for Cellular Metabolism, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK Correspondence to: Paul A. Townsend, e-mail: p.a.townsend@manchester.ac.uk Keywords: annexin A3, migration, neoplasm, biomarker, breast cancer Received: February 06, 2015      Accepted: May 22, 2015      Published: June 04, 2015 ABSTRACT Breast cancers are the most common cancer-affecting women; critically the identification of novel biomarkers for improving early detection, stratification and differentiation from benign tumours is important for the reduction of morbidity and mortality. To identify and functionally characterise potential biomarkers, we used mass spectrometry (MS) to analyse serum samples representing control, benign breast disease (BBD) and invasive breast cancer (IDC) patients. Complementary and multidimensional proteomic approaches were used to identify and validate novel serum markers. Annexin A3 (ANX A3) was found to be differentially expressed amongst different breast pathologies. The diagnostic value of serum ANX A3 was subsequently validated by ELISA in an independent serum set representing the three groups. Here, ANX A3 was significantly upregulated in the benign disease group sera compared with other groups ( P < 0.0005). In addition, paired breast tissue immunostaining confirmed that ANX A3 was abundantly expressed in benign and to a lesser extent malignant neoplastic epithelium. Finally, we illustrated ANX A3 expression in cell culture lysates and conditioned media from neoplastic breast cell lines, and its role in neoplastic breast cell migration in vitro . This study confirms the novel role of ANX A3 as a mammary biomarker, regulator and therapeutic target.