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Hypertonic saline infusion dampens inflammatory responses and suppresses neutrophil-endothelial interaction by reducing adhesion molecule expression. This study tested the hypothesis that hypertonic saline attenuates tumor cell adhesion to the endothelium through a similar mechanism.Human colon cancer cells (LS174T) were transfected with green fluorescent protein and exposed to lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6 under hypertonic and isotonic conditions for 1 and 4 hours. Confluent human umbilical vein endothelial cells were similarly exposed. Cellular apoptosis and expression of adhesion molecules and laminin were measured by flow cytometry. Tumor cell adhesion to endothelium and laminin was assessed with fluorescence microscopy. Data are represented as mean ± standard error of mean, and an ANOVA test was performed to gauge statistical significance, with P < .05 considered significant.Hypertonic exposure significantly reduced tumor cell adhesion despite the presence of the perioperative cell stressors (42 ± 2.9 vs 172.5 ± 12.4, P < .05), attenuated tumor cell β-1 integrin (14.43 vs 23.84, P < .05), and endothelial cell laminin expression (22.78 ± 2.2 vs 33.74 ± 2.4, P < .05), but did not significantly alter cell viability.Hypertonic saline significantly attenuates tumor cell adhesion to endothelium by inhibiting adhesion molecule and laminin expression. This may halt the metastatic behavior of tumor cells shed at surgery.