CHARACTERIZATION OF SOMATOSTATIN RECEPTORS AND GROWTH-INHIBITION BY THE SOMATOSTATIN ANALOG BIM23014 IN SMALL-CELL LUNG-CARCINOMA XENOGRAFT- SCLC-6

Human small cell lung cancer (SCLC) is a neuroendocrine tumour with a very poor prognostic. Receptors for somatostatin-14 and its synthetic analogue BIM23014 (Lanreotide) were characterized in 3 human SCLC xeno grafts (SCLC-6, SCLC-10 and SCLC-75) transplanted in nude mice. The bi nding activity of both iodinated ligands was tested by cross-linking a ssay. One major complex of 57kDa was identified by both ligands in all 3 rumours. Two other minor complexes were only detected by the natura l ligand: 90kDa in all 3 rumours and 70kDa in 2 out of the 3 tumours ( SCLC-6 and SCLC-75). Analysed by Northern hydrization, the expression of the gene encoding for the receptor subtype I was detected in all 3 rumours whereas the expression of the receptor subtype II was only det ected in 2 out of the 3 rumours (SCLC-6 and SCLC-75). No receptor subt ype III transcript was observed. The relative quantification of the de tected messengers and of the cross-linked complexes determined by dens itometry suggested that SCLC-6 contained a large amount of somatostati n receptors. SCLC-6 growing in nude mice was used to evaluate the anti proliferative effect of BIM23014. BIM23014 (250 mu g, b. i. d. for 5 d ays) significantly inhibited tumor growth and had an additive effect w ith cis-platinum (1.5mg/kg/day for 2 days) when given concomitantly. V alues of the relative tumour volume as compared to control were: BIM23 014 alone 57%, cisplatinum alone 57% and BIM23014 + cis-platinum: 78%. These experimental data suggest that BIM23014 given alone or in combi nation with cis-platinum could have a therapeutic potential in the tre atment pf somatostatin receptor positive SCLCs.