Recombinant human stem cell factor does exert minor stimulation of growth in small cell lung cancer and melanoma cell lines.
We have previously reported on the stimulation of clonal growth of a glioblastoma cell line by rhSCF (Berdel et al., Cancer Res 1992, 52, 3498-3502). Within an extensive screening programme of haematopoietic growth factor activity on malignant cells, the effects of rhSCF were further tested on the growth of 29 different human cell lines derived from a wide range of solid tumours, among them six lung cancers and five melanomas. RhSCF (0, 1, 10, 100 ng/ml) was tested in a human tumour cloning assay (HTCA) which reliably detects growth modulation of tumour cells by cytokines. Additionally, a tritiated thymidine uptake test was used. Growth of 27 of the 29 cell lines tested was not affected by rhSCF. However, growth of the small cell lung cancer (SCLC) cell line HTB 120 was slightly stimulated (1.5 fold that of controls), and that of the melanoma cell line MeWo was stimulated up to 1.3-fold. This activity was eliminated dose-dependently by the tyrosine kinase inhibitor, genistein. We further analysed the cell lines for expression of the proto-oncogene C-KIT and its ligand SCF. All melanoma and lung cancer cell lines expressed SCF as assessed at the mRNA level. Northern blotting also revealed clear C-KIT mRNA expression in three melanoma (HAS, MeWo, SK-MEL-28), one NSCLC (HTB 53), and four SCLC cell lines (HTB 119, HTB 120, HTB 171, HTB 175). Furthermore, C-KIT protein expression was detected by flow cytometric analysis on the cell surface of MeWo, HTB 119 and HTB 120 cells. Our data indicate that SCF can be operative in growth modulation of non-haematopoietic malignant cells, especially SCLC and melanoma. However, our extensive screening of SCF/tumour cell interaction shows that this interaction is rare and makes potential hazards, such as tumour stimulation upon clinical use of rhSCF in conjunction with chemotherapy in cancer patients, unlikely for the majority of other tumour histologies.
Papadimitriou
C A
CA
Department of Haematology and Oncology, Universitaetsklinikum Benjamin Franklin (Steglitz), Berlin, Germany.
Topp
M S
MS
Serve
H
H
Oelmann
E
E
Koenigsmann
M
M
Maurer
J
J
Oberberg
D
D
Reufi
B
B
Thiel
E
E
Berdel
W E
WE
D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008545:Melanoma / Q000473:pathology*; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D011519:Proto-Oncogenes / Q000502:physiology; D012334:RNA, Neoplasm / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000473:pathology
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit