The role of cellular motility in the invasion of human neuroblastoma cells with or without N-myc amplification and expression

Background/Purpose: Patients who have neuroblastomas with N-myc amplification that are extremely invasive and result in distant metastases tend to have a very poor prognosis. The authors reported previously that N-myc amplification and expression might be closely related to the invasiveness of human neuroblastoma cells. However, the role of cellular motility has not yet been clarified in the invasion of neuroblastoma cells. The aim of this study was, therefore, to elucidate the role of cellular motility in the invasion of neuroblastoma cells. Methods: Six human neuroblastoma cell lines were used for an invasion assay in vitro using polycarbonate filters coated with basement membrane Matrigel. The amplification and expression of N-myc oncogene was examined by Southern and Northern blotting, respectively. The cellular motility was quantified by computerized image analysis on the morphology of cultured cells. Results: IMR-32, GOTO, and DZ, all of which had N-myc amplification, showed a high degree of invasiveness and a high cellular motility, whereas NB-69 and SK-N-SH without N-myc amplification showed an extremely low degree of invasiveness and cellular motility. ST without N-myc amplification, which was established from an aggressive tumor, showed an exceptionally high degree of motility and invasiveness. A transcriptional reduction of the N-myc gene by retinoic acid (RA) decreased the motility, which thus resulted in a marked decline of invasiveness in IMR-32 and GOTO. Conclusion: The cellular motility correlated with the invasive capacity of human neuroblastoma cells, which thus indicated that cellular motility may play an important role in invasion. J Pediatr Surg 33:1765-1770. Copyright (C) 1998 by W.B. Saunders Company.