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Macrophages mediate colon carcinoma cell adhesion in the rat liver after exposure to lipopolysaccharide.

ABSTRACT: The surgical resection of primary colorectal cancer is associated with an enhanced risk of liver metastases. Moreover, bacterial translocation or anastomic leakage during resection has been shown to correlate with a poor long-term surgical outcome, suggesting that bacterial products may contribute to the formation of metastases. Driven by these premises, we investigated the role of the bacterial product lipopolysaccharide (LPS) in the generation of liver metastases. Intraperitoneal injection of LPS led to enhanced tumor-cell adhesion to the rat liver as early as 1.5 h post-administration. Furthermore, a rapid loss of the expression of the tight junction protein zonula occludens-1 (ZO-1) was observed, suggesting that LPS disrupts the integrity of the microvasculature. LPS addition to endothelial-macrophage co-cultures damaged endothelial monolayers and caused the formation of intercellular gaps, which was accompanied by increased tumor-cell adhesion. These results suggest that macrophages are involved in the endothelial damage resulting from exposure to LPS. Interestingly, the expression levels of of ZO-1 were not affected by LPS treatment in rats in which liver macrophages had been depleted as well as in rats that had been treated with a reactive oxygen species (ROS) scavenger. In both settings, decreased tumor-cell adhesion was observed. Taken together, our findings indicate that LPS induces ROS release by macrophages, resulting in the damage of the vascular lining of the liver and hence allowing increased tumor-cell adherence. Thus, peri-operative treatments that prevent the activation of macrophages and-as a consequence-limit endothelial damage and tumor-cell adhesion may significantly improve the long-term outcome of cancer patients undergoing surgical tumor resection.

SUBMITTER: Gul N

PROVIDER: S-EPMC3525607 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Macrophages mediate colon carcinoma cell adhesion in the rat liver after exposure to lipopolysaccharide.

Gül Nuray N Grewal Simran S Bögels Marijn M van der Bij Gerben J GJ Koppes Malika M A MM Oosterling Steven J SJ Fluitsma Donna M DM Hoeben Kees A KA Beelen Robert H J RH van Egmond Marjolein M

Oncoimmunology 20121201 9

The surgical resection of primary colorectal cancer is associated with an enhanced risk of liver metastases. Moreover, bacterial translocation or anastomic leakage during resection has been shown to correlate with a poor long-term surgical outcome, suggesting that bacterial products may contribute to the formation of metastases. Driven by these premises, we investigated the role of the bacterial product lipopolysaccharide (LPS) in the generation of liver metastases. Intraperitoneal injection of ...[more]

PMID: 23264898

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Project description:BackgroundMicrocirculatory disturbance is closely associated with multiple diseases such as ischemic and septic stroke. Luteolin (3,4,5,7-tetrahydroxyflavone) is a vascular protective flavonoid present in several dietary foods. However, how luteolin plays a role in microcirculatory disturbance is still unknown. The purpose of this study was to find out the influence of luteolin on the lipopolysaccharide (LPS)-induced microcirculatory disturbance, focusing on its effect on leukocyte adhesion and the underlying mechanism of this effect.MethodsAfter injecting LPS into rats, we used an inverted intravital microscope to observe the velocity of red blood cells in venules, numbers of leukocytes adherent to and emigrated across the venular wall, hydrogen peroxide production in venular walls and mast cell degranulation. Intestinal microcirculation blood flow was measured by High-resolution Laser Doppler Perfusion Imaging. Histological changes of small intestine and mesenteric arteries were evaluated. Additionally, cell adhesion stimulated by LPS was tested on EA.hy926 and THP-1 cells. The production of pro-inflammatory cytokines, adhesion molecules and the activation of TLR4/Myd88/NF-κB signaling pathway were determined.ResultsThe results showed luteolin significantly inhibited LPS-induced leukocyte adhesion, hydrogen peroxide production and mast cell degranulation, and increased intestinal microcirculation blood flow and ameliorated pathological changes in the mesenteric artery and the small intestine. Furthermore, luteolin inhibited the release of pro-inflammatory cytokines, the expression of TLR4, Myd88, ICAM-1, and VCAM-1, the phosphorylation of IκB-α and NF-κB/p65 in LPS stimulated EA.hy926.ConclusionsOur findings revealed that it is likely that luteolin can ameliorate microcirculatory disturbance. The inhibitory effects of luteolin on the leukocyte adhesion stimulated by LPS, which participates in the development of microcirculatory disturbance, are mediated through the regulation of the TLR4/Myd88/NF-κB signaling pathway.

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Macrophages mediate colon carcinoma cell adhesion in the rat liver after exposure to lipopolysaccharide.

Publications

Macrophages mediate colon carcinoma cell adhesion in the rat liver after exposure to lipopolysaccharide.

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