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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 (SSR) have been identified in membrane homogenates or tissue sections from several hundred human tumors. SSR have been found in most neuroendocrine tumors, ie, growth hormone (GH)- and thyrotropin (TSH)-producing pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors, paragangliomas, pheochromocytomas, medullary thyroid carcinomas (MTC), and small-cell lung carcinomas. SSR 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 SSR are rather differentiated, eg, astrocytomas in contrast to glioblastomas, but exceptions such as high-grade malignant lymphomas do exist. An inverse relationship exists between SSR 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 SSR characterized by low affinity for the octapeptide SS analogue, octreotide. The function of SSR in human tumors differs according to tumor type; SSR in pituitary and GEP tumors mediate hormone secretion inhibition and possibly have some antiproliferative effects. However, in meningiomas, activation of SSR inhibits forskolin-stimulated adenylate cyclase activity and weakly stimulates proliferation. Although SSR seem to mediate antiproliferative effects in animal models and cell lines of lymphomas and 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 (SSR) are present in many human tumors, particularly neuroendocrine types. Their function varies, with some SSR subtypes showing potential antiproliferative effects in certain cancers.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Somatostatin receptors (SSR) are widely expressed in various human tumors.
- SSR are commonly found in neuroendocrine tumors, lymphomas, brain tumors, and breast tumors.
Purpose of the Study:
- To investigate the presence and subtypes of somatostatin receptors in human tumors.
- To explore the functional roles of SSR in different tumor types.
Main Methods:
- Analysis of membrane homogenates and tissue sections for SSR expression.
- Characterization of SSR subtypes and their affinity for ligands like octreotide.
- Assessment of SSR functional effects, including hormone secretion inhibition and proliferation modulation.
Main Results:
- SSR identified in numerous human tumors, including pituitary, gastroenteropancreatic, paragangliomas, pheochromocytomas, medullary thyroid carcinomas, small-cell lung, lymphomas, meningiomas, astrocytomas, and breast tumors.
- Inverse relationship between SSR and epidermal growth factor receptors in lung, glial, and breast tumors; co-expression in meningiomas.
- Specific SSR subtypes with low octreotide affinity found in ovarian tumors, MTC, and insulinomas.
Conclusions:
- SSR expression is a common feature across a broad spectrum of human malignancies.
- The functional impact of SSR in tumors is diverse, mediating hormone inhibition and potentially antiproliferative effects, though this requires further validation in primary human tumors.