Peritumoral expression of adipokines and fatty acids in breast cancer

Ann Surg Oncol. 2013 Dec;20 Suppl 3:S731-8. doi: 10.1245/s10434-013-3274-1. Epub 2013 Sep 20.

Abstract

Background: Adipokines in the tumor microenvironment may contribute to cancer growth. We hypothesized that peritumoral fat can be a source of lipid-derived energy for tumors by increasing adipose triglyceride lipase (ATGL)-mediated lipolysis and down-regulating a negative regulator of adipogenesis, pigment epithelium-derived factor (PEDF).

Methods: In a pilot study, tissue from mastectomies (n = 19) was collected from sites both adjacent (peritumoral) and distant to the tumor for comparison of ATGL, PEDF, and leptin expression levels using immunohistochemistry. Statistical analysis was performed by Student's t test to determine significance.

Results: Mean tumor size was 2.4 cm, and 10 (59 %) patients had tumor-positive nodes. Mean body mass index (BMI) was 28.1 kg/m(2). ATGL expression was significantly increased in obese patients (BMI ≥ 30 kg/m(2)) compared with the nonobese group (P < 0.04). Leptin expression was increased in the peritumoral stroma of obese patients compared with distant sites (P = 0.03). Peritumoral PEDF and the leptin/PEDF ratio were significantly affected by tumor size and node status. Tumors ≥ 2 cm had lower peritumoral stromal expression of PEDF than tumors <2 cm (P = 0.01). In node-positive cases, expression of PEDF was significantly decreased in the peritumoral stroma compared with node-negative cases (1.22 vs. 1.80, P < 0.04). The leptin/PEDF ratio was markedly elevated in the peritumoral region of node-positive cases versus node-negative cases (2.17 vs. 1.18, P < 0.001).

Conclusions: Peritumoral expression of adipokines was altered in both obesity and more advanced breast tumors, suggesting a role for adipokines in enhancing tumor growth. Future studies should focus on the use of adipokines as biomarkers.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / metabolism*
  • Adipose Tissue / metabolism*
  • Adipose Tissue / pathology
  • Adult
  • Biomarkers, Tumor / metabolism*
  • Body Mass Index
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / secondary
  • Carcinoma, Intraductal, Noninfiltrating / metabolism
  • Carcinoma, Intraductal, Noninfiltrating / secondary
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / secondary
  • Cell Proliferation
  • Eye Proteins / metabolism
  • Fatty Acids / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Leptin / metabolism
  • Lipase / metabolism
  • Lymphatic Metastasis
  • Mastectomy
  • Middle Aged
  • Neoplasm Staging
  • Nerve Growth Factors / metabolism
  • Obesity / metabolism*
  • Obesity / pathology
  • Pilot Projects
  • Prognosis
  • Serpins / metabolism
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Adipokines
  • Biomarkers, Tumor
  • Eye Proteins
  • Fatty Acids
  • Leptin
  • Nerve Growth Factors
  • Serpins
  • pigment epithelium-derived factor
  • Lipase
  • PNPLA2 protein, human