Expression of stem cell factor and c-kit in human neuroblastoma. The Children's Cancer Group.
During development, mice with mutations of stem cell factor (SCF) or its receptor c-kit exhibit defects in melanogenesis, as well as hematopoiesis and gonadogenesis. Because melanocytes derive from neural crest cells, the role of SCF and c-kit was investigated in the neural crest-derived childhood tumor neuroblastoma. Using reverse transcription-polymerase chain reaction analysis, simultaneous expression of steady-state mRNA for the SCF ligand and its receptor c-kit was found in 14 of 14 (100%) human neuroblastoma cell lines and clones and in 8 of 18 (45%) human neuroblastoma tumor samples. Functional blockade of c-kit receptors in the cell lines SK-N-BE(2) and SH-SY5Y using the mouse monoclonal anti-c-kit antibody SR-1 resulted in a significant decrease in cellular growth rate when measured by either 3H-thymidine incorporation or clonogenicity. In addition, higher levels of c-kit mRNA expression were associated with parental neuroblastoma cell lines and subclones with a neuronal (N) differentiation phenotype, whereas lower levels of c-kit mRNA were associated with neuroblastoma cell line subclones having a schwannian/glial/melanocytic pattern of differentiation. However, the differentiation phenotype of neuroblastoma cell lines was not directly altered when c-kit expression was blocked using the SR-1 antibody. In summary, these data indicate that c-kit receptor expression may play a significant role in the growth regulation of the two neuroblastoma cell lines examined and suggest that c-kit may also play a similar role in neuroblastoma growth regulation in vivo. Simultaneous expression of SCF and c-kit mRNA in both neuroblastoma cell lines and tumors implies that c-kit may act as part of an autocrine growth loop in conjunction with endogenous production of SCF in this disease.
Cohen
P S
PS
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA.
Chan
J P
JP
Lipkunskaya
M
M
Biedler
J L
JL
Seeger
R C
RC
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000096:biosynthesis; D015870:Gene Expression; D016298:Hematopoietic Cell Growth Factors / Q000096:biosynthesis*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D018241:Neuroectodermal Tumors, Primitive, Peripheral; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019009:Proto-Oncogene Proteins c-kit; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D016184:Receptors, Colony-Stimulating Factor / Q000096:biosynthesis*; D019089:Stem Cell Factor; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004273:DNA, Neoplasm; D016298:Hematopoietic Cell Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D013936:Thymidine