EVALUATION OF SOMATOSTATIN BIOSYNTHESIS, SOMATOSTATIN RECEPTORS AND TUMOR-GROWTH IN MURINE MEDULLARY-THYROID CARCINOMA

Spontaneous medullary thyroid carcinomas (MTCs) of old rat thyroids we re analyzed for the expression of somatostatin and somatostatin bindin g sites in tumoral C cells in relation to the stage of tumor developme nt, the mitotic activity of tumoral tissue and calcitonin biosynthesis as a marker of C cell differentiation. High levels of both immunoreac tive somatostatin and its mRNA were detected in a subpopulation of tum oral C cells, gathered in areas suggesting a clonal proliferation and located preferentially at the periphery of the tumor. These cells also displayed high levels of calcitonin and its mRNA. However, many calci tonin immunoreactive cells showed no sign of somatostatin synthesis. T he proliferative activity of the somatostatin-containing areas was low and slow compared to the areas lacking somatostatin production. Howev er, it increased during the course of tumor growth. Somatostatin bindi ng sites, measured with in vitro receptor autoradiography using I-125- [Tyr(3)]- octreotide or I-125-[Leu(8), dTrp(22), Tyr(25)]SS-28, were n ot detected in any of the MTCs tested. In rat MTC cells, somatostatin was associated with differentiation and slow proliferation, two parame ters inversely correlated with the progression of malignancy. As expec ted, owing to the highly regulated secretion of the differentiated end ocrine cell type, its presence was correlated with low basal calcitoni n levels. However, the absence of somatostatin binding sites on any ty pe of MTC cells does not favor a direct autocrine regulation of this p eptide in this murine model of human MTC.