AUTHOR=Rosendahl Ann H. , Bergqvist Malin , Lettiero Barbara , Kimbung Siker , Borgquist Signe 

TITLE=Adipocytes and Obesity-Related Conditions Jointly Promote Breast Cancer Cell Growth and Motility: Associations With CAP1 for Prognosis

JOURNAL=Frontiers in Endocrinology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00689

DOI=10.3389/fendo.2018.00689

ISSN=1664-2392

ABSTRACT=<p>The global increase in overweight and obesity rates represent pressing public health concerns associated with severe comorbidities, amongst a rising incidence and impaired outcome of breast cancer. Yet, biological explanations for how obesity affects breast cancer are incompletely mapped. Herein, the joint impact by differentiated 3T3-L1 adipocytes and obesity-related metabolic conditions on breast cancer cells was evaluated <italic>in vitro</italic> and adipocyte-derived mediators assessed. Adipokine receptor expression was explored among breast cancer cell lines (<italic>n</italic> = 47) and primary breast tumors (<italic>n</italic> = 1,881), where associations with survival outcomes were investigated. Adipocytes and metabolic complications jointly stimulated breast cancer cell proliferation and motility, with phenotype-specific differences. Resistin was among the top modulated adipokines secreted by 3T3-L1 adipocytes under obesity-associated metabolic conditions compared with normal physiology. The newly identified resistin receptor, CAP1, was expressed across a large panel of breast cancer cell lines and primary breast tumors. <italic>CAP1</italic> was associated with poor tumor characteristics with higher <italic>CAP1</italic> expression among estrogen receptor (ER)-negative tumors, relative to ER-positive tumors (<italic>P</italic> = 0.025), and higher histological grades (<italic>P</italic> = 0.016). High <italic>CAP1</italic> tumor expression was associated with shorter overall survival (adjusted hazard ratio [HR<sub>adj</sub>] 1.54; 95% confidence interval [CI], 1.11–2.13) and relapse-free survival (HR<sub>adj</sub> 1.47; 95% CI, 1.10–1.96), compared with low or intermediate <italic>CAP1</italic> expression, particularly among ER-positive tumors or lymph node positive tumors. Together, these translational data demonstrate that the adipocyte secretome promote breast cancer cell proliferation and motility and highlight a potential role of CAP1 regarding breast cancer outcome—results that warrant further investigation to elucidate the obesity-breast cancer link in human pathology.</p>