Reduced expression of transforming growth factor-beta receptor type III inhigh stage neuroblastomas

Transforming growth factor beta (TGF-beta) is a powerful inhibitor of cell proliferation and a potent inducer of differentiation, Resistance to TGF-be ta action is a characteristic of many malignancies and has been attributed to alterations of TGF-beta receptors as well as disturbance of downstream t ransduction pathways. To analyse the TGF-beta response in neuroblastoma, th e expression of TGF-beta 1 and TGF-beta type I, II and III receptor genes w as investigated in 61 cancer samples by means of reverse transcription poly merase chain reaction. The specimens analysed belong to different stages, n amely nine samples of stage 1, ten of stage 2, nine of stage 3 and 28 of st age 4. Moreover, five samples were of stage 4S, which represents a tumour f orm undergoing spontaneous regression. The results obtained show that TGF-b eta 1 and TGF-beta type I and II receptor genes appear to be almost equally expressed in neuroblastomas of all stages. Conversely, TGF-beta type III r eceptor gene expression, which is required for an efficacious TGF-beta bind ing and function, is strongly reduced exclusively in neuroblastomas of stag es 3 and 4, These findings were directly confirmed by immunohistochemical a nalyses of ten neuroblastoma specimens. Our results suggest the occurrence of an altered TGF-beta response in advanced neuroblastomas which might be a n important mechanism for escaping growth control and for developing invasi veness. Moreover, our findings allow the proposal of a novel mechanism, nam ely down-regulation of TGF-beta type III receptor gene expression, to avoid TGF-beta inhibitory activity (C) 2000 Cancer Research Campaign.