STEM-CELL FACTOR SUPPRESSES APOPTOSIS IN NEUROBLASTOMA CELL-LINES

Stem cell factor (SCF) is a glycoprotein growth factor produced by mar row stromal cells that acts after binding to its specific surface rece ptor, which is the protein encoded by the protooncogene c-kit. SCF syn ergizes with specific lineage factors in promoting the proliferation o f primitive hematopoietic progenitors, and has been administered to ex pand the pool of these progenitors in cancer patients treated with hig h-dose chemotherapy. SCF and its c-kit receptor are expressed by some tumor cells, including myeloid leukemia, breast carcinoma, small cell lung carcinoma, melanoma, gynecological tumors, and testicular germ ce ll tumors. Previous studies of SCF in neuroblastoma have produced conf licting conclusions. To explore the role of SCF in neuroblastoma, we s tudied five neuroblastoma lines (IMR-5, SK-N-SH, SK-N-BE, AF8, and SJ- N-KP) and the neuroepithelioma line CHP-100. All lines expressed mRNA for c-kit and c-kit protein at low intensity as measured by flow cytom etry, and secreted SCF in medium culture as shown by ELISA. Exogenous SCF did not modify H-3 thymidine uptake in the neuroblastoma and neuro epithelioma cell lines. After 6 days' culture in the presence of anti- c-kit, the number of viable neuroblastoma cells was significantly lowe r than the control, and terminal deoxynucleotidyl transferase assay sh owed a substantial increase of apoptotic cells: The percentage of posi tive cells was 1-3% in the control lines, whereas in the presence of a nti c-kit it varied from 29% of SK-N-BE to 92% of CHP-100. After 9 day s' culture in the presence of anti-c-kit, no viable cells were detecta ble. These data indicate that SCF is produced by some neuroblastoma ce ll lines via an autocrine loop to protect them from apoptosis.