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In vitro detection of somatostatin receptors in human tumors
J C Reubi1, E Krenning, S W Lamberts
1Sandoz Research Institute Bern, Switzerland.
Abstract:
Somatostatin receptors (SS-R) have been identified in membrane homogenates 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Somatostatin receptors (SS-R) are present in many human tumors, particularly neuroendocrine types. Their function varies, potentially inhibiting hormone secretion and proliferation, but antiproliferative effects in human tumors require further study.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Somatostatin receptors (SS-R) are expressed in numerous human tumors, including neuroendocrine, brain, breast, and lung cancers.
- Expression patterns and functions of SS-R vary significantly across different tumor types.
- An inverse relationship between SS-R and epidermal growth factor receptors is observed in several cancers.
Purpose of the Study:
- To investigate the presence and function of somatostatin receptors in a wide range of human tumors.
- To explore the correlation between SS-R expression and tumor differentiation.
- To examine the potential antiproliferative effects of SS-R activation in human cancers.
Main Methods:
- Analysis of SS-R expression in membrane homogenates and tissue sections from human tumors.
- Characterization of SS-R subtypes and their affinity for somatostatin analogs.
- Assessment of SS-R function, including hormone secretion modulation and effects on cellular pathways.
Main Results:
- SS-R are prevalent in neuroendocrine tumors (pituitary, GEP, paragangliomas, pheochromocytomas, MTC, SCLC), lymphomas, meningiomas, astrocytomas, and breast tumors.
- Most SS-R expressing tumors are well-differentiated, with exceptions like high-grade lymphomas.
- Tumor-specific functions of SS-R include hormone inhibition (pituitary, GEP) and modulation of adenylate cyclase activity (meningiomas).
Conclusions:
- Somatostatin receptors are widely expressed in human tumors, with diverse functional roles.
- While SS-R activation shows antiproliferative potential in preclinical models, this needs robust validation in human primary tumors.
- Further research is warranted to elucidate the precise role of SS-R in tumor biology and therapeutic strategies.
