COEXPRESSION OF STEM-CELL FACTOR AND ITS RECEPTOR C-KIT IN HUMAN-MALIGNANT GLIOMA CELL-LINES

Stem cell factor (SCF), a hematopoietic growth factor, is the Ligand o f the tyrosine kinase receptor encoded by the c-kit proto-oncogene. Be side the important role of this receptor-ligand complex in hematopoies is, gametogenesis and melanogenesis, SCF and its receptor have been sh own to be expressed in the brain. We have studied the expression of SC F and c-kit in 20 human malignant glioma cell lines at the mRNA as wel l as at the protein level. In addition, recombinant human (rh) SCF was tested in [H-3]thymidine uptake assays for a mitogenic effect on thes e cells. SCF and c-Kit proteins were detected in the cytoplasm of glio ma cells by alkaline phoshatase-monoclonal anti-alkaline phosphatase i mmunostaining and Western blot analysis. However, neither SCF nor c-Ki t were seen on the cell surface by flow cytometry. Further more, none of the proliferation assays showed a mitogenic effect for exogenously added rhSCF. Blocking studies using an anti-SCF antibody failed to dem onstrate modulating effects on the growth of selected cell lines. Thes e results suggest that SCF and c-Kit may mediate non-proliferative sig nals or may employ intracellular mechanisms for autocrine growth regul ation of glioma cells.