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

• Published in: Frontiers in endocrinology (Lausanne) Vol. 9; p. 689
• Main Authors: Rosendahl, Ann H, Bergqvist, Malin, Lettiero, Barbara, Kimbung, Siker, Borgquist, Signe
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 22.11.2018
• Subjects: adipocytes; Basic Medicine; breast cancer; Cancer and Oncology; Cancer och onkologi; CAP1; Cell and Molecular Biology; Cell- och molekylärbiologi; Clinical Medicine; Endocrinology; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; metabolic conditions; obesity; prognosis; CAP1; breast cancer; metabolic conditions; adipocytes; prognosis; obesity
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2018.00689

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 and adipocyte-derived mediators assessed. Adipokine receptor expression was explored among breast cancer cell lines ( = 47) and primary breast tumors ( = 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. was associated with poor tumor characteristics with higher expression among estrogen receptor (ER)-negative tumors, relative to ER-positive tumors ( = 0.025), and higher histological grades ( = 0.016). High tumor expression was associated with shorter overall survival (adjusted hazard ratio [HR ] 1.54; 95% confidence interval [CI], 1.11-2.13) and relapse-free survival (HR 1.47; 95% CI, 1.10-1.96), compared with low or intermediate 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.