Secretome analysis of breast cancer-associated adipose tissue to identify paracrine regulators of breast cancer growth
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Lapeire Lore1,2, Hendrix An2,3, Lecoutere Evelyne4, Van Bockstal Mieke4, Vandesompele Jo2,5, Maynard Dawn6, Braems Geert7, Van Den Broecke Rudy7, Müller Cathérine8, Bracke Marc3, Cocquyt Véronique1, Denys Hannelore1,2 and De Wever Olivier2,3
1Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
2Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium
3Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium
4Department of Pathology, Ghent University Hospital, Ghent, Belgium
5Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
6Medical Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland, USA
7Department of Gynecology, Ghent University Hospital, Ghent, Belgium
8Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, UPS, Toulouse, France
De Wever Olivier, email: firstname.lastname@example.org
Keywords: adipose tissue, breast cancer, proliferation, secretome, palbociclib
Received: November 01, 2016 Accepted: April 17, 2017 Published: May 03, 2017
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.
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