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 extablished 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 patter, and fibrinolytic activity of these cell lines and of previously extablished 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 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.

[1]  J. T. Wachsman,et al.  Fibrinolytic activity associated with human neuroblastoma cells. , 1974, Experimental cell research.

[2]  S. Das,et al.  Human neuroblastoma in nude mice. , 1975, Cancer research.

[3]  R. Sparkes,et al.  Cellulose acetate electrophoresis of human glucose-6-phosphate dehydrogenase. , 1969, The Journal of laboratory and clinical medicine.

[4]  J. Young,et al.  Incidence of malignant tumors in U. S. children. , 1975, The Journal of pediatrics.

[5]  L. Ossowski,et al.  Fibrinolysis associated with oncogenic transformation. Morphological correlates. , 1974, The Journal of biological chemistry.

[6]  M. Seabright A rapid banding technique for human chromosomes. , 1971, Lancet.

[7]  W. Benedict,et al.  Relationship between fibrinolysis of cultured cells and malignancy. , 1975, Journal of the National Cancer Institute.

[8]  M. Tannenbaum Ultrastructural pathology of adrenal medullary tumors. , 1970, Pathology annual.

[9]  H. Harris,et al.  Esterase D: a new human polymorphism , 1973, Annals of human genetics.

[10]  H. Herschman,et al.  Adrenergic, cholinergic, and inactive human neuroblastoma cell lines with the action-potential Na+ ionophore. , 1977, Cancer research.

[11]  W. W. Nichols,et al.  Definition of a continuous human cell line derived from neuroblastoma. , 1970, Cancer research.

[12]  W. Benedict,et al.  Recent advances in molecular pathology: a review. Some aspects of chromosome changes in cancer. , 1969, Experimental and molecular pathology.

[13]  M. Nirenberg,et al.  Sodium uptake associated with activation of action potential ionophores of cultured neuroblastoma and muscle cells. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Peter A. Jones,et al.  Fibrinolytic activity in a human fibrosarcoma cell line and evidence for the induction of plasminogen activator secretion during tumor formation , 1975, Cell.

[15]  H. Harris,et al.  Adenosine deaminase polymorphism in man , 1968 .

[16]  P. Moorhead,et al.  Establishment and characterization of human neuroblastoma cell lines. , 1976, Cancer research.

[17]  B. Spengler,et al.  Metaphase chromosome anomaly: association with drug resistance and cell-specific products. , 1976, Science.

[18]  N. Breslow,et al.  Statistical estimation of prognosis for children with neuroblastoma. , 1971, Cancer research.

[19]  L. Fink,et al.  In vitro correlates of transformation in C3H/10T1/2 clone 8 mouse cells. , 1976, Cancer research.

[20]  W. Russell,et al.  A simple cytochemical technique for demonstration of DNA in cells infected with mycoplasmas and viruses , 1975, Nature.

[21]  M. Saier,et al.  Relationship of cell growth behavior in vitro to tumorigenicity in athymic nude mice. , 1976, Cancer research.

[22]  B. Spengler,et al.  Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. , 1973, Cancer research.

[23]  D. Hopkinson Genetic Markers in Human Blood. By ELOISE R. GIBLETT , 1970 .