BMP2/BMPR1A is linked to tumour progression in dedifferentiated liposarcomas

O’Neill, H.L., Cassidy, A.P., Harris, O.B. and Cassidy, J.W. (2016) BMP2/BMPR1A is linked to tumour progression in dedifferentiated liposarcomas. PeerJ, 4, e1957. (doi: 10.7717/peerj.1957) (PMID:27114889) (PMCID:PMC4841227)

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Abstract

Bone Morphogenic Protein 2 (BMP2) is a multipurpose cytokine, important in the development of bone and cartilage, and with a role in tumour initiation and progression. BMP2 signal transduction is dependent on two distinct classes of serine/threonine kinase known as the type I and type II receptors. Although the type I receptors (BMPR1A and BMPR1B) are largely thought to have overlapping functions, we find tissue and cellular compartment specific patterns of expression, suggesting potential for distinct BMP2 signalling outcomes dependent on tissue type. Herein, we utilise large publicly available datasets from The Cancer Genome Atlas (TCGA) and Protein Atlas to define a novel role for BMP2 in the progression of dedifferentiated liposarcomas. Using disease free survival as our primary endpoint, we find that BMP2 confers poor prognosis only within the context of high BMPR1A expression. Through further annotation of the TCGA sarcoma dataset, we localise this effect to dedifferentiated liposarcomas but find overall BMP2/BMP receptor expression is equal across subsets. Finally, through gene set enrichment analysis we link the BMP2/BMPR1A axis to increased transcriptional activity of the matrisome and general extracellular matrix remodelling. Our study highlights the importance of continued research into the tumorigenic properties of BMP2 and the potential disadvantages of recombinant human BMP2 (rhBMP2) use in orthopaedic surgery. For the first time, we identify high BMP2 expression within the context of high BMPR1A expression as a biomarker of disease relapse in dedifferentiated liposarcomas.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cassidy, Professor James
Authors: O’Neill, H.L., Cassidy, A.P., Harris, O.B., and Cassidy, J.W.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:PeerJ
Publisher:PeerJ
ISSN:2167-8359
ISSN (Online):2167-8359
Published Online:19 April 2016
Copyright Holders:Copyright © 2016 O’Neill et al.
First Published:First published in PeerJ 4:e1957
Publisher Policy:Reproduced under a Creative Commons License

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