Tumor growth factor expression in obesity and changes in expression with weight loss: another cause of increased virulence and incidence of cancer in obesity.
BACKGROUND
Obesity is associated with increased tumorigenesis. Previously, we demonstrated that inflammation in obesity caused cancer fighting cells to display greater surface receptor levels, predisposing them to early cell death. We measured the inflammatory tumor growth factor levels to determine whether inflammation in obesity increases expression of these factors, potentially predisposing these patients to greater rates of neoplasia.


METHODS
A total of 24 patients undergoing weight loss surgery had samples collected preoperatively and at 6 and 12 months after surgery. The growth factors analyzed included tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, vascular endothelial growth factor, hepatocyte growth factor, TNF-receptor I (TNF-RI), TNF-RII, death receptor 5, leptin, and adiponectin. Control samples were obtained from 10 healthy, normal weight volunteers.


RESULTS
The tumor growth factors TNF-α, TNF-RI, TNF-RII, vascular endothelial growth factor, hepatocyte growth factor, interferon-γ, IL-2, IL-5, and IL-6 all decreased significantly (P <.05) compared with the preoperative values. The IL-4, IL-8, leptin, death receptor 5, adiponectin, and granulocyte-macrophage colony-stimulating factor levels did not change significantly over time. The IL-1b and IL-10 levels were less than the detection limit at all points. When obese patient serum was compared with healthy volunteer pooled serum, we found that the leptin, death receptor 5, hepatocyte growth factor, vascular endothelial growth factor, TNF-RI, TNF-RII, TNF-α, IFN-γ, granulocyte-macrophage colony-stimulating factor, IL-4, IL-5, IL-6, and IL-8 levels were all 2-37 times greater than the levels in the controls at baseline. The concentrations of these same growth factors had decreased levels only 1-3.5 times greater than those of the controls at 12 months postoperatively.


CONCLUSIONS
Many inflammatory tumor growth factors are present in greater concentrations in obese individuals. This could explain the greater prevalence of neoplasia in the morbidly obese population.
Cottam
Daniel
D
Surgical Weight Loss Center of Utah, Salt Lake City, Utah 84102, USA. drdanielcottam@yahoo.com
Fisher
Barry
B
Ziemba
Amy
A
Atkinson
James
J
Grace
Brian
B
Ward
David C
DC
Pizzorno
Giuseppe
G
D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D004198:Disease Susceptibility; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D015431:Weight Loss
D052242:Adiponectin; D007378:Interleukins; D020738:Leptin; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor