EXPRESSION OF STEM-CELL FACTOR AND ITS RECEPTOR BY HUMAN NEUROBLASTOMA-CELLS AND TUMORS

Bone marrow (BM) is a frequent site of metastasis in children with neu roblastoma (NB). Nonhematopoietic cell lines of the same neuroectoderm al origin produce both stem cell factor (SCF) and its receptor, the pr oduct of the c-kit protooncogene (c-kit). Because recombinant SCF is l ikely to be soon clinically tested to accelerate BM recovery after hig h-dose chemotherapy, a treatment administered to children with dissemi nated NB, we addressed the question of whether SCF/c-kit complex could play a role in the proliferation and metastasis of NB cells. Northern blot analysis showed SCF mRNA transcripts in 7 of 8 (88%) NB cell lin es and c-kit in 1 (13%). Neither c-kit nor SCF could be detected by We stern blotting in cell extracts or by surface immunofluorescence and f low cytometry. Soluble SCF protein was detected by enzyme immunoassay at low concentrations in the cell supernatants in the same 7 NB cell l ines. Treatment of 4 NB cell lines by SCF +/- cytokines relevant to BM physiology did not induce c-kit antigenic expression or modulate H-3- thymidine uptake. Likewise, the latter was not changed by incubating t he cells with anti-c-kit neutralizing antibodies. Immunohistochemical analysis showed weak diffuse or focal staining for SCF and c-kit in fe w primary or metastatic tumor samples, only once simultaneously. We co nclude that NB cell lines usually produce low levels of soluble SCF bu t do not express c-kit and that both proteins are rarely detected in N B tumors. The SCF/c-kit complex appears to be unlikely to stimulate NB growth or metastasis; thus, recombinant SCF could be safely administe red to children with NB. (C) 1995 by The American Society of Hematolog y.