Coexpression of stem cell factor and its receptor c-Kit in human malignant glioma cell lines

Abstract

Stem cell factor (SCF), a hematopoietic growth factor, is the ligand of the tyrosine kinase receptor encoded by the c-kit proto-oncogene. Beside the important role of this receptor-ligand complex in hematopoiesis, gametogenesis and melanogenesis, SCF and its receptor have been shown to be expressed in the brain. We have studied the expression of SCF and c-kit in 20 human malignant glioma cell lines at the mRNA as well as at the protein level. In addition, recombinant human (rh) SCF was tested in [3H]thymidine uptake assays for a mitogenic effect on these cells. SCF and c-Kit proteins were detected in the cytoplasm of glioma cells by alkaline phosphatase-monoclonal anti-alkaline phosphatase immunostaining and Western blot analysis. However, neither SCF nor c-Kit were seen on the cell surface by flow cytometry. Furthermore, none of the proliferation assays showed a mitogenic effect for exogenously added rhSCF. Blocking studies using an anti-SCF antibody failed to demonstrate modulating effects on the growth of selected cell lines. These results suggest that SCF and c-Kit may mediate non-proliferative signals or may employ intracellular mechanisms for autocrine growth regulation of glioma cells.

Astrocyte apoptosis induced by HIV-1 transactivation of the c -kit protooncogene

“…The frequency of apoptosis in c-Kit-positive HIV-1 Nef-positive astrocytes (Fig. 1f ) To investigate the link between c-Kit overexpression and astrocyte apoptosis, we transfected the astrocyte-derived cell line U87, which expresses endogenous c-Kit (30) (Fig. 1 b and c), with the c-Kit expression plasmid pcKit.…”

Cytokines and tumors of the central nervous system

“…Human glioblastoma cell lines constitutively produce SCF and c-Kit mRNA (Stanulla et al, 1995;Tada et al, 1994a), suggesting the existence of an autocrine growth loop. However, for 28 glioblastoma cell lines tested, anti-SCF antibodies did not block cell growth, and only one cell line (CRL1620) was growth-stimulated by the addition of exogenous human SCF (Berdel et al, 1992;Stanulla et al, 1995).…”

Tumor-intrinsic and -extrinsic roles of c-Kit: mast cells as the primary off-target of tyrosine kinase inhibitors

“…Belong to this group cases of small cell lung cancer (Krystal et al, 1996), adenoid cystic carcinoma (Freier et al, 2005), colon carcinoma (Bellone et al, 2006), and brain tumors (Gomes et al, 2007). c-Kit mutations are rare in these neoplasms, but in several cases autocrine loops have been described, in which tumors are able to provide c-Kit stimulation by producing SCF themselves (Stanulla et al, 1995;Krystal et al, 1996;Bellone et al, 2006). Breast cancer.…”