In vitro Detection of Somatostatin Receptors in Human Tumors

Somatostatin receptors (SS-R) have been identified in membrane homoge-nates or tissue sections from several hundred human tumors. SS-R have been found in most neuroendocrine tumors, i.e. GH- and TSH-producing pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors, paragangliomas, pheochromocytomas, medullary thyroid carcinomas (MTC) and small cell lung carcinomas. SS-R have also been found in the majority of malignant lymphomas, in several brain tumors (all meningiomas, most astrocytomas) and in breast tumors. The majority of tumors expressing SS-R are rather differentiated, e.g. astrocytomas in contrast to glioblastomas, but exceptions exist such as high grade malignant lymphomas. An inverse relationship exists between SS-R and receptors for epidermal growth factor in lung tumors, glial tumors and most breast tumors, whereas meningiomas express both receptors simultaneously. A minority of tumors such as ovarian tumors, MTC and insulinomas, express a subtype of SS-R, characterized by low affinity for the octapeptide SS analog octreotide. The function of SS-R in human tumors differs according to tumor type, SS-R in pituitary and GEP tumors mediate hormone secretion inhibition, and have possibly some antiproliferative effects. In meningiomas, however, activation of SS-R inhibits forskolin-stimulated adenylate cyclase activity, and weakly stimulates proliferation. Although SS-R seem to mediate antiproliferative effects in animal models and cell lines of lymphomas, breast and lung tumors, such an effect has not yet been convincingly documented in human primary tumors. The clinical implications of the presence of SS-R in tumors are: as a predictive marker for efficient therapy with octreotide in pituitary and GEP tumors, as a diagnostic marker: for pathobiochemical classification of tumors, using in vitro detection methods, as a diagnostic marker for clinical evaluation using in vivo scanning techniques, as a prognostic marker, and as a potential target for radiotherapy.