Peritumoral expression of adipokines and fatty acids in breast cancer.
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.
Department of Surgery, University of Chicago Medical Center, Chicago, IL, USA, Jennifer.Gnerlich@uchospitals.edu.
Jennifer L
JL
Gnerlich
Katharine A
KA
Yao
Philip S
PS
Fitchev
Robert A
RA
Goldschmidt
Michael C
MC
Bond
Mona
M
Cornwell
Susan E
SE
Crawford
D054392:Adipokines / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000556:secondary; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000556:secondary; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000556:secondary; D049109:Cell Proliferation; D005136:Eye Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D020738:Leptin / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008207:Lymphatic Metastasis; D008408:Mastectomy; D008875:Middle Aged; D009367:Neoplasm Staging; D009414:Nerve Growth Factors / Q000378:metabolism; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D010865:Pilot Projects; D011379:Prognosis; D015843:Serpins / Q000378:metabolism; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D000099174:Pigment Epithelium-Derived Factor; D000217:Acyltransferases
D054392:Adipokines; D014408:Biomarkers, Tumor; D005136:Eye Proteins; D005227:Fatty Acids; D020738:Leptin; D008049:Lipase; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C494794:PNPLA2 protein, human; D000217:Acyltransferases