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pubmed-article:15386356pubmed:abstractTextIn this experimental study, the influence of surgery-induced proinflammatory cytokines on tumor recurrence in the lung was investigated. A reproducible human in vitro assay was developed to study the adhesion of HT29 colon carcinoma cells to monolayers of microvascular endothelial cells of the lung (HMVECs-L) or human umbilical venous endothelial cells (HUVECs). Preincubation of HMVECs-L with maximally active concentrations of IL-1beta and TNF-alpha, but not with IL-6, resulted in at least 250% adhesion compared to control adhesion (p <or= 0.01). The effect of IL-1beta and TNF-alpha was concentration- and time-dependent. Comparable results were found for HUVECs. Tumor cell adhesion was not increased after preincubation of HT29 with TNF-alpha. Enzyme immunoassays of cytokine-preincubated HUVECs and HMVECs-L showed concentration- and time-dependent upregulation of E-selectin, ICAM-1 and VCAM-1 expression. In addition, LFA-1 and VLA-4 were only expressed on HMVECs-L, creating more binding possibilities for HMVECs-L compared to HUVECs. Inhibition assays with anti-E-selectin monoclonal antibody significantly decreased tumor cell adhesion to HUVECs; however, it did not affect tumor cell adhesion to HMVECs-L. Furthermore, anti-ICAM-1 and anti-VCAM-1 antibodies did not affect adhesion. Our results prove IL-1beta and TNF-alpha promote tumor cell adhesion to HMVECs-L in vitro and may therefore account for enhanced tumor recurrence in the lung seen after major surgical trauma. The adhesion of HT29 to HUVEC is inhibitable by E-selectin antibodies, whereas the adhesion to HMVEC-L is not inhibitable by these antibodies. Probably not one but a complex of adhesion molecules is responsible for enhanced adhesion to HMVECs-L.lld:pubmed
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pubmed-article:15386356pubmed:articleTitleInfluence of proinflammatory cytokines on the adhesion of human colon carcinoma cells to lung microvascular endothelium.lld:pubmed
pubmed-article:15386356pubmed:affiliationDepartment of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands.lld:pubmed
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