ACQUIRED TGF-BETA(1) SENSITIVITY AND TGF-BETA(1) EXPRESSION IN CELL-LINES ESTABLISHED FROM A SINGLE SMALL-CELL LUNG-CANCER PATIENT DURING CLINICAL PROGRESSION

Three small cell lung cancer cell lines established from a single pati ent during longitudinal follow-up were examined for in vitro expressio n of TGF beta and TGF beta receptors, i.e. the components of an autocr ine loop. GLC 14 was established prior to treatment, GLC 16 on relapse after chemotherapy and GLC 19 on recurrence after radiotherapy. TGF b eta was detected by ELISA and TGF beta receptors by chemical crosslink ing to radiolabelled TGF beta(1). Furthermore, TGF beta and TGF beta r eceptor mRNAs were detected by northern blot analysis. Expression of t ype II TGF beta receptor mRNA and protein was found in GLC 16 and GLC 19. These cell lines were also growth inhibited by exogenously adminis trated TGF beta(1). TGF beta(1) mRNA and protein in its latent form wa s only expressed in the radiotherapy-resistant cell line, GLC 19. The results indicate that disease progression in this patient was parallel ed by a gain in sensitivity to the growth inhibition by TGF beta(1) du e to type II TGF beta receptor, and a gain of latent TGF beta(1) prote in. Lack of type II receptor expression in GLC 14, which was also resi stant to growth inhibition by exogenous TGF beta(1), was not due to gr oss structural changes in the type II receptor gene, as examined by So uthern blotting. Also, the type I receptor could not be detected by li gand binding assay in this cell line, despite expression of mRNA for t his receptor. This agrees with previous findings that type I receptor cannot bind TGF beta(1) without coexpression of the type II receptor.