Original Research ARTICLE
Adipocytes and obesity-related conditions jointly promote breast cancer cell growth and motility: associations with CAP1 for prognosis
- 1Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Sweden
- 2Department of Oncology, Aarhus University Hospital, Denmark
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 in vitro and adipocyte-derived mediators assessed. Adipokine receptor expression was explored among breast cancer cell lines (n=47) and primary breast tumors (n=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. CAP1 was associated with poor tumor characteristics with higher CAP1 expression among estrogen receptor (ER)-negative tumors, relative to ER-positive tumors (P=0.025), and higher histological grades (P=0.016). High CAP1 tumor expression was associated with shorter overall survival (adjusted hazard ratio [HRadj] 1.54; 95% confidence interval [CI], 1.11-2.13) and relapse-free survival (HRadj 1.47; 95% CI, 1.10-1.96), compared with low or intermediate CAP1 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.
Keywords: breast cancer, Obesity, Adipocytes, CAP1, Metabolic conditions, prognosis
Received: 12 Jul 2018;
Accepted: 02 Nov 2018.
Edited by:Antimo Migliaccio, Università degli Studi della Campania "Luigi Vanvitelli" Naples, Italy
Reviewed by:Eva Surmacz, Temple University, United States
Roger Moorehead, University of Guelph, Canada
Copyright: © 2018 Rosendahl, Bergqvist, Lettiero, Kimbung and Borgquist. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: PhD. Ann H. Rosendahl, Lund University, Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund, Sweden, firstname.lastname@example.org