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Title: Aberrant pregnancy-associated plasma protein-A expression in breast cancers prognosticates clinical outcomes.
Austin Authors: Prithviraj, Prashanth;Anaka, Matthew;Thompson, Erik W;Sharma, Revati;Walkiewicz, Marzena;Tutuka, Candani S A;Behren, Andreas;Kannourakis, George;Jayachandran, Aparna
Affiliation: Olivia Newton-John Cancer Research Institute
Gallipoli Medical Research Institute and The University of Queensland, Brisbane, Australia
School of Cancer Medicine, La Trobe University, Victoria, Australia
Translational Research Institute, Woolloongabba, Australia
Fiona Elsey Cancer Research Institute, Ballarat Technology Park- Central Suite 23, 106-110 Lydiard St Sth, Ballarat, VIC, 3350, Australia
Department of Medicine, University of Melbourne, Victoria, Australia
Department of Medicine, University of Alberta, Alberta, Canada
Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Australia
Federation University Australia, Ballarat, VIC, Australia
Issue Date: 13-Aug-2020
Date: 2020-08-13
Publication information: Scientific Reports 2020; 10(1): 13779
Abstract: Elevated levels of pregnancy-associated plasma protein-A (PAPP-A) have been implicated in the pathogenesis of various malignancies, including breast cancers. Breast cancer is one of the most frequent carcinomas and is the second most common cancer type detected in women of child-bearing age. Throughout pregnancy PAPP-A is produced and secreted by the placental syncytiotrophoblast cells; co-incidentally pregnancy-associated breast cancers often have an aggressive clinical course. The components of the PAPP-A/IGF axis was assessed in a panel of breast cancer cell lines. Using neutralising antibodies the impact of PAPP-A/IGF axis on cell motility was evaluated. PAPP-A was expressed in four of the twelve breast cancer cell lines tested. Blocking PAPP-A and IGFBP4 with neutralising antibodies significantly decreased motiliy of MDA-MB-231 cells. Upregulation of PAPP-A expression in breast tumours resulted in a trend towards worse overall survival. Notably, PAPP-A expression also positively correlated with epithelial-to-mesenchymal transition markers. In conclusion, these results indicate that PAPP-A plays an important role in breast cancer progression and it may be a promising therapeutic target in breast cancer.
DOI: 10.1038/s41598-020-70774-9
ORCID: 0000-0001-5329-280X
Journal: Scientific Reports
PubMed URL: 32792532
Type: Journal Article
Appears in Collections:Journal articles

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