The “don't eat me” signal CD47 is a novel diagnostic biomarker and potential therapeutic target for diffuse malignant mesothelioma

Schürch, Christian; Forster, Stefan; Brühl, Frido; Yang, Sara Hsin-Yi; Felley-Bosco, Emanuela; Hewer, Ekkehard (2017). The “don't eat me” signal CD47 is a novel diagnostic biomarker and potential therapeutic target for diffuse malignant mesothelioma. Oncoimmunology, 7(1), e1373235. Taylor & Francis 10.1080/2162402X.2017.1373235

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Diffuse malignant mesothelioma (DMM) is one of the prognostically most discouraging cancers with median survivals of only 12–22 months. Due to its insidious onset and delayed detection, DMM is often at an advanced stage at diagnosis and is considered incurable. Combined chemo- and radiotherapy followed by surgery only marginally affect outcome at the cost of significant morbidity. Because of the long time period between exposure to asbestos and disease onset, the incidence of DMM is still rising and predicted to peak around 2020. Novel markers for the reliable diagnosis of DMM in body cavity effusion specimens as well as more effective, targeted therapies are urgently needed. Here, we show that the “don't eat me” signalling molecule CD47, which inhibits phagocytosis by binding to signal regulatory protein α on macrophages, is overexpressed in DMM cells. A two-marker panel of high CD47 expression and BRCA1-associated protein 1 (BAP-1) deficiency had a sensitivity of 78% and specificity of 100% in discriminating DMM tumour cells from reactive mesothelial cells in effusions, which is superior to the currently used four-marker combination of BAP-1, glucose transporter type 1, epithelial membrane antigen and desmin. In addition, blocking CD47 inhibited growth and promoted phagocytosis of DMM cell lines by macrophages in vitro. Furthermore, DMM tumours in surgical specimens from patients as well as in a mouse DMM model expressed high levels of CD47 and were heavily infiltrated by macrophages. Our study demonstrates that CD47 is an accurate novel diagnostic DMM biomarker and that blocking CD47 may represent a promising therapeutic strategy for DMM.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Schürch, Christian; Forster, Stefan; Brühl, Frido; Yang, Sara Hsin-Yi and Hewer, Ekkehard

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2162-4011

Publisher:

Taylor & Francis

Language:

English

Submitter:

Ekkehard Hewer

Date Deposited:

04 Oct 2017 11:33

Last Modified:

12 Jan 2018 08:06

Publisher DOI:

10.1080/2162402X.2017.1373235

PubMed ID:

29296529

BORIS DOI:

10.7892/boris.105265

URI:

https://boris.unibe.ch/id/eprint/105265

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