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 g lioblastoma cell line by rhSCF (Berdel et al., Cancer Res 1992, 52, 34 98-3502). Within an extensive screening programme of haematopoietic gr owth factor activity on malignant cells, the effects of rhSCF were fur ther tested on the growth of 29 different human cell lines derived fro m 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 cl oning assay (HTCA) which reliably detects growth modulation of tumour cells by cytokines. Additionally, a tritiated thymidine uptake test wa s used. Growth of 27 of the 29 cell lines tested was not affected by r hSCF. However, growth of the small cell lung cancer (SCLC) cell line H TB 120 was slightly stimulated (1.5 fold that of controls), and that o f the melanoma cell line MeWo was stimulated up to 1.3-fold, This acti vity was eliminated dose-dependently by the tyrosine kinase inhibitor, genistein. We further analysed the cell lines for expression of the p roto-oncogene C-KIT and its ligand SCF. All melanoma and lung cancer c ell lines expressed SCF as assessed at the mRNA level. Northern blotti ng also revealed clear C-KIT mRNA expression in three melanoma (HAS, M eWo, 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 wa s detected by flow cytometric analysis on the cell surface of MeWo, HT B 119 and HTB 120 cells. Our data indicate that SCF can be operative i n 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 h azards, such as tumour stimulation upon clinical use of rhSCF in conju nction with chemotherapy in cancer patients, unlikely for the majority of other tumour histologies.