EXPRESSION OF STEM-CELL FACTOR AND C-KIT IN HUMAN NEUROBLASTOMA

During development, mice with mutations of stem cell factor (SCF) or i ts receptor c-kit exhibit defects in melanogenesis, as well as hematop oiesis 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-po lymerase chain reaction analysis, simultaneous expression of steady-st ate 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 rec eptors in the cell lines SK-N-BE(2) and SH-SY5Y using the mouse monocl onal anti-c-kit antibody SR-1 resulted in a significant decrease in ce llular growth rate when measured by either H-3-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 hav ing a schwannian/glial/melanocytic pattern of differentiation. However , the differentiation phenotype of neuroblastoma cell lines was not di rectly altered when c-kit expression was blocked using the SR-1 antibo dy. In summary, these data indicate that c-kit receptor expression may play a significant role in the growth regulation of the two neuroblas toma cell lines examined and suggest that c-kit may also play a simila r role in neuroblastoma growth regulation in vivo. Simultaneous expres sion 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 con junction with endogenous production of SCF in this disease. (C) 1994 b y The American Society of Hematology.