BACKGROUND: The relationship between obesity and cancer has become of particular interest due to the rapidly growing prevalence of overweight individuals. Obesity predisposes individuals to the development of hepatic steatosis and is an independent risk factor for several neoplasms. Toll-like receptor 4 (TLR4) is the innate receptor for endotoxin, and steatotic livers are known to be sensitive to endotoxin. TLR4 signaling has been shown to have proneoplastic effects in vitro due to its effect on immune surveillance. Thus far, studies have predominantly focused on the effect of tumor-cell-derived TLR4 without regard to host TLR4 signaling. RESULTS: In the present study we show that steatotic livers have increased expression of TLR4. Obese animals developed higher metastatic tumor burden in the liver than lean controls regardless of the presence or absence of intact host TLR4. After silencing TLR4 expression using RNAi in the mouse colon cancer cell line MC38, there was a significant decrease in metastatic tumor burden within the liver of obese animals. CONCLUSIONS: These findings demonstrate that steatotic livers have increased susceptibility to metastatic tumor growth and that silencing tumor cell TLR4 reduces metastatic tumor burden in steatotic liver.
BACKGROUND: The relationship between obesity and cancer has become of particular interest due to the rapidly growing prevalence of overweight individuals. Obesity predisposes individuals to the development of hepatic steatosis and is an independent risk factor for several neoplasms. Toll-like receptor 4 (TLR4) is the innate receptor for endotoxin, and steatotic livers are known to be sensitive to endotoxin. TLR4 signaling has been shown to have proneoplastic effects in vitro due to its effect on immune surveillance. Thus far, studies have predominantly focused on the effect of tumor-cell-derived TLR4 without regard to host TLR4 signaling. RESULTS: In the present study we show that steatotic livers have increased expression of TLR4. Obese animals developed higher metastatic tumor burden in the liver than lean controls regardless of the presence or absence of intact host TLR4. After silencing TLR4 expression using RNAi in the mousecolon cancer cell line MC38, there was a significant decrease in metastatic tumor burden within the liver of obese animals. CONCLUSIONS: These findings demonstrate that steatotic livers have increased susceptibility to metastatic tumor growth and that silencing tumor cell TLR4 reduces metastatic tumor burden in steatotic liver.
Authors: Lisa Volk-Draper; Kelly Hall; Caitlin Griggs; Sandeep Rajput; Pascaline Kohio; David DeNardo; Sophia Ran Journal: Cancer Res Date: 2014-10-01 Impact factor: 12.701
Authors: Sarbjeet Makkar; Terrence E Riehl; Baosheng Chen; Yan Yan; David M Alvarado; Matthew A Ciorba; William F Stenson Journal: Mol Cancer Ther Date: 2019-09-04 Impact factor: 6.261
Authors: Hamza O Yazdani; Eva Roy; Alexander J Comerci; Dirk J van der Windt; Hongji Zhang; Hai Huang; Patricia Loughran; Sruti Shiva; David A Geller; David L Bartlett; Allan Tsung; Tai Sheng; Richard L Simmons; Samer Tohme Journal: Cancer Res Date: 2019-09-13 Impact factor: 12.701
Authors: E L Wang; Z R Qian; M Nakasono; T Tanahashi; K Yoshimoto; Y Bando; E Kudo; M Shimada; T Sano Journal: Br J Cancer Date: 2010-02-09 Impact factor: 7.640