General anaesthetics reduce acute lymphoblastic leukaemia cell migration and homing in vitro and in vivo via CXCR4 and osteopontin mediated mechanisms

Background: Acute lymphoblastic leukaemia (ALL) is the most common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL treatments but their effects on ALL malignancy remain unknown. Herein, we aim to study the effect of two commonly used general anaesthetics, intravenous propofol and inhalational sevoflurane, on the migration and homing of ALL cells in vitro and in vivo. Methods: NALM-6 cells were treated with propofol (5 and 10μg/ml) or sevoflurane (3.6%) in vitro for 6 hours. Then, cells were harvested for flow cytometry analysis. For in vitro migration experiments, NALM-6 cells were pre-treated with propofol and sevoflurane for 6 hours before being loaded on to upper chamber of migration chamber and then cells were collected in the lower chamber after 6 hours of migration. For in vitro adhesion assay, NALM-6 cells were pre-treated with propofol and sevoflurane before adhesion assay was carried out. In in vitro experiments, GFP-NALM-6 cells were pre-treated with propofol (10μg/ml) or sevoflurane (3.6%) for 6 hours. Then, cells were injected intravenously to mice followed by intravital microscopy. Results: Both anaesthetics reduced in vitro migration, in vivo migration and in vivo homing as expressed by 1) the reduction in number of cells entering bone marrow and 2) disturbance in homing location in relative to the nearest endosteal surface. Upon further investigation, it was revealed that the expression of surface CXCR4 in vitro and in vitro adhesion to thrombin cleaved osteopontin (OPN) were reduced by general anaesthetics. Those changes might result in the changes of migration and homing. Conclusion: Together, our data suggest that both propofol and sevoflurane could reduce ALL migration and homing in vivo and in vitro via CXCR4 and OPN mediated mechanisms