The response of mesothelial cells to surgical trauma and bacterial contamination is poorly defined. We have recently shown that CO2 pneumoperitoneum increases systemic metastasis of neuroblastoma cells in a murine model. Thus, we hypothesized that CO2 alters the morphology and function of mesothelial cells and facilitates transmesothelial tumor cell migration.
Materials and methods
Murine mesothelial cells were exposed to 100% CO2 and 5% CO2 as control. Scanning electron microscopy (SEM) investigations, as well as LPS-induced granulocyte-colony stimulating factor (G-CSF) production and mitochondrial activity (MTT assay) were measured. Transmesothelial migration of neuroblastoma cells (Neuro2a) was determined using a transwell chamber system.
CO2 incubation was associated with a significant destruction of the microvillar formation in SEM. Migration studies showed that the barrier function of the mesothelial monolayer decreased. A significantly increased migration of neuroblastoma cells was identified after 100% CO2 exposure (P < 0.05). Although the conversion of MTT as an indicator of mitochondrial activity was only slightly and not significantly reduced after CO2 incubation, the release of G-CSF induced by LPS was completely blocked during the incubation with 100% CO2 (P < 0.05). The capacity of G-CSF release recovered after the incubation.
We observed that peritoneal mesothelial cells lose their typical cell morphology by CO2 incubation, which is accompanied by facilitated migration of neuroblastoma cells. Moreover, the synthesis of immunological factors is blocked, but this effect is not long lasting. These mechanisms may explain an increased metastasis rate of neuroblastoma cells after CO2 pneumoperitoneum, which was recently observed in a murine model.
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