title: Annexin A3 is a mammary marker and a potential neoplastic breast cell therapeutic target.
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.
authors.affiliation: Cancer Sciences Unit, University of Southampton, Southampton, UK.
authors.forename: Bashar
authors.initials: B
authors.lastname: Zeidan
authors.affiliation: Faculty Institute for Cancer Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.|Manchester Centre for Cellular Metabolism, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Jackson
authors.affiliation: Cancer Sciences Unit, University of Southampton, Southampton, UK.
authors.forename: Samantha E T
authors.initials: SE
authors.lastname: Larkin
authors.affiliation: Cancer Sciences Unit, University of Southampton, Southampton, UK.
authors.forename: Ramsey I
authors.initials: RI
authors.lastname: Cutress
authors.affiliation: St. George's Medical Biomics Centre, St. George's University of London, London, UK.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Coulton
authors.affiliation: Cancer Sciences Unit, University of Southampton, Southampton, UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Ashton-Key
authors.affiliation: Cancer Sciences Unit, University of Southampton, Southampton, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Murray
authors.affiliation: Cancer Sciences Unit, University of Southampton, Southampton, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Packham
authors.affiliation: Faculty Institute for Cancer Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.|Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece.|Manchester Centre for Cellular Metabolism, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Gorgoulis
authors.affiliation: Cancer Sciences Unit, University of Southampton, Southampton, UK.
authors.forename: Spiros D
authors.initials: SD
authors.lastname: Garbis
authors.affiliation: Cancer Sciences Unit, University of Southampton, Southampton, UK.|Faculty Institute for Cancer Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.|Manchester Centre for Cellular Metabolism, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Townsend
mesh_terms: D000368:Aged; D017318:Annexin A3 / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D013058:Mass Spectrometry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned; D017318:Annexin A3
keywords: Annexin A3; biomarker; breast cancer; migration; neoplasm