PRODUCTION AND PRECLINICAL SIGNIFICANCE OF HEMATOPOIETIC PEPTIDE GROWTH-FACTORS (HPGF) IN HUMAN NONSEMINOMATOUS GERM-CELL TUMOR-CELL LINES

Peptide growth factors involved in the regulation of haematopoiesis (H PGF), for example granulocyte-colony-stimulating factor (G-CSF) and gr anulocyte/macrophage-colony-stimulating factor (GM-CSF), are of clinic al importance in the treatment of testicular germ cell tumour (GCT) pa tients with modern chemotherapy regimens since they ameliorate chemoth erapy-induced neutropenia. Aberrant expression of and/or response to H PGF has been reported in several solid tumour types although no data a re available on GCT with the exception of those on stem cell factor (S CF). The aims of this pre-clinical study were twofold: (1) to screen a panel of human non-seminomatous (NS)GCT for the production of HPGF an d (2) to test the effects of G-CSF or SCF on the growth of NSGCT cell lines in vitro, and on the growth kinetics of two human NSGCT xenograf t models. HPGF concentrations in cell culture supernatant from 11 NSGC T cell lines growing under routine culture conditions were measured by enzyme-linked immunosorbent assay. The growth kinetics of cell lines was quantified in vitro using the sulphorhodamine B assay. The growth kinetics of nude mouse NSGCT xenografts was followed by measuring tumo ur volumes every 2-3 days over days 1-30, following daily subcutaneous injection of nude mice (days 1-14). The cell lines produced G-CSF (1/ 11 cell lines), GM-CSF (2/11), SCF (2/11), M-CSF (6/11), and interleuk in-6 (9/11). Growth stimulation of cell line H12.1 by SCF was observed in vitro, but. no statistically significant differences in NSGCT xeno graft tumour volume (V-T) Or relative V-T (rV(T)) in treated groups we re observed on days 14 or 29 compared to the control. The change in rV (T) of H12.1 xenografts treated with C-CSF alone compared to control ( rV(T)/rV(T,c),) was 0.96 on day 29. The values for rV(T)/rV(T,c) for H 12.1 xenografts treated with G-CSF in combination with low- or high-do se SCF were, respectively, 1.67 or 1.7 compared to 1.19 for SCF-treate d mice. The results are in agreement with clinical data to date where no observations have been reported of stimulation or inhibition of tum ours in patients receiving treatment with G-CSF. Before any clinical t rials are initiated in GCT patients treated with G-CSF in combination with SCF, further pre-clinical experiments with this tumour type are r ecommended to investigate this phenomenon further in a greater number of NSGCT cell lines in vitro and in vivo and with a wider range of SCF /G-CSF schedules. The potential relevance of secretion of HPGF in NSGC T cell lines in vitro to the pathobiology of GCT in patients is also a subject of interest for future research.