Cytomegalovirus infection as a possible progression factor in neuroblastoma disease

Background: There is evidence that the infection with human cytomegalovirus is clinically associated with enhanced metastasis and progression of neuro blastoma disease, An in vitro model with HCMV-infected neuroblastoma cells (NB) was used to investigate whether HCMV modulates the metastatic potentia l of NB. Methods: The neuroblastoma cell line UKF-NB-4 and its productively and pers istently HCMV-infected variant UKF-NB-4(AD169) were cocultured with human e ndothelial cells (EC). The rate of NB adherent to the endothelial monolayer and the rate of transmigrating NB was determined by means of combined refl exion interference contrast/phase contrast microscopy. Results: UKF-NB-4(AD169) adhered to and transmigrated through cocultured EC monolayer to a significantly higher extent compared with the non-infected cell line UKF-NB-4, At the cell-to-cell contact sites between UKF-NB-4(AD16 9) and EC the intercellular endothelial contacts loosened resulting in the formation of reversible focal openings in the monolayer. This phenomenon wa s not observed with UKF-NB-4. The transendothelial migration rate of UKF-NB -4(AD169) was therefore significantly higher than that of UKF-NB-4, The for mation of focal openings in the endothelial monolayer and the enhanced tran smigration rate of UKF-NB-4(AD169) was suppressed in the presence of phenan troline, suggesting that HCMV-induced proteinases might be responsible for this phenomenon. Conclusion: The results confirm our assumption that HCMV has the ability to modulate functional properties of NB which are essential for the interacti ons with endothelial cells and thus for metastasation. The clinical relevan ce of these findings has to be further defined yet by means of prospective studies with HCMV-infected neuroblastoma patients, Proteinase inhibitors co uld be valuable in the therapeutic treatment of these patients.