EXPRESSION OF INSULIN-LIKE GROWTH-FACTORS (IGFS), THEIR RECEPTORS ANDIGF BINDING PROTEIN-3 IN NORMAL, BENIGN AND MALIGNANT SMOOTH-MUSCLE TISSUES

To assess the role of insulin-like growth factors (IGF-s) in growth an d transformation of normal (myometrium) and tumorous smooth muscle cel l (SMC) tissues, in situ hybridization (ISH) analysis for insulin-like growth factor I and II (IGF-I and IGF-II) mRNAs was combined with det ection of IGF peptides, their receptors and IGF binding protein-3 (IGF BP-3), mRNAs for both IGFs were detected in smooth muscle cells in nor mal, benign and malignant SMC tissues, together with the IGF peptides, both IGF receptors and IGFBP-3. This suggests an autocrine role for b oth IGFs. Leiomyomas had higher IGF-I peptide levers and higher levels of type I IGF receptors than myometrium, supporting the idea that IGF s play a role in the growth and transformation of these tumours. Low-g rade leiomyosarcomas contained more IGF-II mRNAs than myometrium and l eiomyoma, fewer type II IGF/mannose 6-phosphate receptors and less IGF BP-3 than myometrium and, in addition, fewer IGF-I mRNAs and type I IG F receptors than leiomyoma. Intermediate- and high-grade leiomyosarcom as had intermediate levels of IGF-II mRNAs and peptide, ranging betwee n those in myometrium and low-grade leiomyosarcomas. Thus, growth and transformation of leiomyosarcomas may be regulated by IGF-II, although more markedly in low-grade than in high-grade leiomyosarcomas. In con clusion, the various categories of SMC tissues are associated with a d istinct expression pattern of the IGF system. This suggests that each category of SMC tumours arises as a distinct entity and that there is no progression of transformation in these tissues.