SOMATOSTATIN RECEPTORS IN HUMAN PROSTATE AND PROSTATE-CANCER

Benign as well as malignant human prostatic tissues were evaluated for their content of somatostatin (SRIH) receptors (SRIH-R). In vitro rec eptor autoradiography techniques on cryostat sections were performed u sing I-125-labeled [Tyr(3)]octreotide as well as I-125-labeled [Leu(8) ,D-Trp(22),Tyr(25)]SRIH-28 as radioligands. SRIH-R were identified in all normal and hyperplastic prostates in the smooth muscles of the str oma, whereas the glands did not express the receptors. Muscular nodule s were strongly receptor positive as well. The receptors were of high affinity (K-d = 0.4 nmol/L) and high specificity for biologically acti ve SRIH analogs; high affinity for SRIH-14, SRIH-28, and octreotide wa s detected, suggesting the presence of the SSTR2 receptor subtype. In situ hybridization studies confirmed the presence of SSTR2 messenger r ibonucleic acid in these tissues. Primary prostate cancers did not hav e SRIH-R identified with I-125-labeled [Tyr(3)]octreotide. However, th ey were expressing SRIH-R identified with I-125-labeled [Leu(8),D-Trp( 22),Tyr(25)]SRIH-28, with a high affinity for SRIH-14 and SRIH-28, but low affinity for octreotide. The receptors were located on tumoral ce lls. In situ hybridization studies revealed a preferential expression of SSTR1. Primary human prostate cancers, therefore, express a differe nt SRIH-R subtype than benign prostate tissue. Several veins and the g anglion cells from the prostatic plexus in the surroundings of the tum ors were expressing SRIH-R with high affinity for octreotide as well. These data suggest that the human prostate as well as prostate cancers mag be targets for SRIH therapy; however, SRIH analogs with different selectivities for SRIH-R subtypes are required in each case.