Morphology, Growth, Chromosomal Pattern, and Fibrinolytic Activity of two New Human Neuroblastoma Cell Lines

Neuroblastoma cell lines LA-N-1 and LA-N-2 were established from neuroblastoma cells in the bone marrow and in the primary tumor, respectively, of two children with metastatic neuroblastoma. Morphology, growth in vitro and in athymic nude mice, chromosomal pattern, and fibrinolytic activity of these cell lines and of previously established human neuroblastoma cell lines IMR-32, SK-N-MC, and SK-N-SH were compared. Most LA-N-1 cells were tear-drop shaped, small cells with processes; they tended to grow in clusters. LA-N-2 was comprised of elongated cells and small round cells, the latter growing in dense clumps on the former. Electron microscopy revealed numerous cytoplasmic dense cores in many LA-N-1 cells but none in LA-N-2 cells. During logarithmic growth in vitro, doubling times for LA-N-1, LA-N-2, SK-N-MC, SK-N-SH, and IMR-32 cells were 32, 56, 23, 36, and 26 hr, respectively. Cells of all lines formed colonies in soft agar, and, after variable latency periods, LA-N-1, LA-N-2, SK-N-MC, and IMR-32 cells formed tumors in athymic nude mice. The marker chromosome(s) characteristic of each cell line was present in more than 90% of cells of a given line. Significant plasminogen-dependent fibrinolytic activity was present in cells of all lines. These studies indicate that LA-N-1 and LA-N-2 cells arose from single but different aberrant progenitor cells and that they have properties of neuroblastoma cells. They also demonstrate that cell lines derived from human neuroblastomas are heterogenous as are the tumors in children.