Peritumoral adipose tissue as a source of inflammatory and angiogenic factors in colorectal cancer.
OBJECTIVE
Obesity is a risk factor for the development of human colorectal cancer (CC). The aim of this work is to report the inflammatory and angiogenic scenario in lean (BMI < 25 kg/m2) and obese (BMI > 30 kg/m2) patients with and without CC and to assess the role of peritumoral adipose tissue in CC-induced inflammation.


METHODS
Patients were divided in four experimental groups: obese patients with CC (OB-CC), lean patients with CC (LEAN-CC), obese patients without CC (OB), and lean patients without CC (LEAN).


RESULTS
Plasma levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-4, IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in OB-CC patients. Peritumoral adipose tissue (TF) explants and cultured mature adipocytes secreted higher amounts of nitrites and nitrates than did control and non-tumoral (NTF) adipose tissue both alone and in response to lipopolysaccharide (LPS). Nitrite and nitrate secretion was also increased in TF explants from OB-CC patients compared with that from LEAN-CC patients. Gene expression of adiponectin, tumor necrosis factor alpha (TNF-α), insulin-like growth factor type I (IGF-I), cyclooxygenase-2 (COX-2), and peroxisome proliferator-activated receptor γ (PPAR-γ) was increased in TF explants from CC patients. LPS increased the gene expression of IL-6, IL-10, TNF-α, vascular endothelial growth factor (VEGF), and COX-2 in OB and in TF explants from OB-CC patients. COX-2 and PPAR-γ inhibition further increased LPS-induced release of nitrites and nitrates in TF explants and adipocytes from OB-CC patients.


CONCLUSIONS
In conclusion, OB-CC patients have increased plasma levels of pro-inflammatory and angiogenic factors. TF from OB-CC patients shows an increased secretion of inflammatory markers compared with both TF from LEAN-CC and non-tumoral adipose tissue (AT) through a COX-2- and PPAR-γ-independent mechanism.
S
S
Amor
M C
MC
Iglesias-de la Cruz
E
E
Ferrero
O
O
García-Villar
V
V
Barrios
N
N
Fernandez
L
L
Monge
A L
AL
García-Villalón
M
M
Granado
D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism*; D015992:Body Mass Index; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D052246:Cyclooxygenase 2 Inhibitors / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D055014:Granulocyte-Macrophage Progenitor Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D009389:Neovascularization, Pathologic; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics
D052242:Adiponectin; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D009566:Nitrates; D009573:Nitrites; D047495:PPAR gamma; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I