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

## TL;DR

This study shows that general anesthetics like propofol and sevoflurane can reduce the spread and movement of leukemia cells in lab and animal models.

## Contribution

The study reveals a novel mechanism by which general anesthetics affect leukemia cell migration and homing via CXCR4 and osteopontin.

## Key findings

- Propofol and sevoflurane reduced in vitro and in vivo migration of ALL cells.
- Both anesthetics decreased CXCR4 expression and adhesion to osteopontin in leukemia cells.
- Anesthetic treatment altered the homing location of leukemia cells in bone marrow.

## Abstract

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 10 μg/ml) or sevoflurane (3.6%)
in vitro for six 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 six hours before being loaded onto the upper chamber of a migration chamber and cells were collected in the lower chamber after six hours of migration. For
in vitro adhesion assays, NALM-6 cells were pre-treated with propofol and sevoflurane before an adhesion assay was carried out.
For in vivo experiments, GFP-NALM-6 cells were pre-treated with propofol (10 μg/ml) or sevoflurane (3.6%) for six hours. Then, cells were injected intravenously into C57BL/6 female mice followed by intravital microscopy.

Results

Both anaesthetics reduced
in vitro migration,
in vivo migration and
in vivo homing, as exemplified by 1) the reduction in the number of cells entering the bone marrow and 2) the disturbance in homing location in relation to the nearest endosteal surface. Our results indicated that general anaesthetics reduced the surface CXCR4 expression. In addition, the adhesion of leukaemia cells to thrombin cleaved osteopontin (OPN) was reduced by general anaesthetics. Those changes might result in the alterations in 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.