Article

The host inflammatory response promotes liver metastasis by increasing tumor cell arrest and extravasation.

Department of Surgery, McGill University Health Cener and Royal Victoria Hospital, Quebec, Canada.
American Journal Of Pathology (impact factor: 4.89). 06/2007; 170(5):1781-92. DOI:10.2353/ajpath.2007.060886
Source: PubMed

ABSTRACT Inflammation can play a regulatory role in cancer progression and metastasis. Previously, we have shown that metastatic tumor cells entering the liver trigger a proinflammatory response involving Kupffer cell-mediated release of tumor necrosis factor-alpha and the up-regulation of vascular endothelial cell adhesion receptors, such as E-selectin. Here, we analyzed spatio-temporal aspects of the ensuing tumor-endothelial cell interaction using human colorectal carcinoma CX-1 and murine carcinoma H-59 cells and a combination of immunohistochemistry, confocal microscopy, and three-dimensional reconstruction. E-selectin expression was evident mainly on sinusoidal vessels by 6 and 10 hours, respectively, following H-59 and CX-1 inoculation, and this corresponded to a stabilization of the number of tumor cells within the sinuses. Tumor cells arrested in E-selectin(+) vessels and appeared to flatten and traverse the vessel lining, away from sites of intense E-selectin staining. This process was evident by 8 (H-59) and 12 (CX-1) hours after inoculation, coincided with increased endothelial vascular cell adhesion molecule-1 expression, and involved tumor cell attachment in areas of intense vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 expression. Nonmetastatic (human) MIP-101 and (murine) M-27 cells induced a weaker response and could not be seen to extravasate. The results show that metastatic tumor cells can alter the hepatic microvasculature and use newly expressed endothelial cell receptors to arrest and extravasate.

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Keywords

cancer progression
 
E-selectin expression
 
endothelial cell receptors
 
endothelial vascular cell adhesion molecule-1 expression
 
ensuing tumor-endothelial cell interaction
 
hepatic microvasculature
 
human colorectal carcinoma CX-1
 
intense E-selectin staining
 
intense vascular cell adhesion molecule-1
 
Kupffer cell-mediated release
 
metastatic tumor cells
 
murine carcinoma H-59 cells
 
platelet endothelial cell adhesion molecule-1 expression
 
proinflammatory response
 
sinusoidal vessels
 
tumor cell attachment
 
Tumor cells
 
tumor necrosis factor-alpha
 
vascular endothelial cell adhesion receptors
 
weaker response