Secretome analysis of breast cancer-associated adipose tissue to identify paracrine regulators of breast cancer growth

// Lapeire Lore 1, 2 , Hendrix An 2, 3 , Lecoutere Evelyne 4 , Van Bockstal Mieke 4 , Vandesompele Jo 2, 5 , Maynard Dawn 6 , Braems Geert 7 , Van Den Broecke Rudy 7 , Müller Cathérine 8 , Bracke Marc 3 , Cocquyt Véronique 1 , Denys Hannelore 1, 2 and De Wever Olivier 2, 3 1 Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium 2 Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium 3 Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium 4 Department of Pathology, Ghent University Hospital, Ghent, Belgium 5 Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium 6 Medical Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland, USA 7 Department of Gynecology, Ghent University Hospital, Ghent, Belgium 8 Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, UPS, Toulouse, France Correspondence to: De Wever Olivier, email: olivier.dewever@ugent.be Keywords: adipose tissue, breast cancer, proliferation, secretome, palbociclib Received: November 01, 2016 Accepted: April 17, 2017 Published: May 03, 2017 ABSTRACT Adipose tissue secretes a plethora of adipokines as evidenced by characterization of subcutaneous and visceral adipose tissue secretomes. However, adipose tissue composition and secretion pattern is depot and disease dependent, influencing the adipose tissue secretome. We investigated the secretome of cancer-associated adipose tissue (CAAT) explants from breast cancer patients and explored its role in breast cancer proliferation. CAAT proteins were identified by LC-MS/MS and human protein antibody arrays and stimulated proliferation of three breast cancer cell lines. Kinomics and transcriptomics of MCF-7 breast cancer cells treated with the secretome of CAAT revealed activation of Akt-, ERK- and JNK-pathways and differential expression of activator protein 1 (AP-1) and cAMP responsive element-binding protein (CREB) target genes. The cyclin-dependent kinase (CDK)4/6-inhibitor palbociclib significantly abrogated CAAT-enhanced breast cancer cell proliferation. Our work characterizes the specific breast CAAT protein secretome and reveals its pro-proliferative potency in breast cancer.