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

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...

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Bibliographic Details
Published in:Oncotarget 2017-07, Vol.8 (29), p.47239-47249
Main Authors: Lapeire, Lore, Hendrix, An, Lecoutere, Evelyne, Van Bockstal, Mieke, Vandesompele, Jo, Maynard, Dawn, Braems, Geert, Van Den Broecke, Rudy, Müller, Cathérine, Bracke, Marc, Cocquyt, Véronique, Denys, Hannelore, De Wever, Olivier
Format: Article
Language:English
Subjects:
Adipose Tissue - pathology
Adipose Tissue - secretion
Antineoplastic Agents - pharmacology
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Line, Tumor
Cell Proliferation - drug effects
Cyclic AMP Response Element-Binding Protein - metabolism
Female
Humans
Metabolomics - methods
Paracrine Communication
Piperazines - pharmacology
Protein Kinase Inhibitors - pharmacology
Proteomics - methods
Pyridines - pharmacology
Research Paper
Transcription Factor AP-1 - metabolism
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.17592