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Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications
J C Reubi1, J Laissue, E Krenning
1Sandoz Research Institute Berne Ltd., Switzerland.
Abstract:
Somatostatin receptors (SS-R) have been identified in membrane homogenates or tissue sections from several hundred tumors. SS-R were 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 were also expressed in a 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 (i.e. astrocytomas vs glioblastomas), but exceptions exist (high grade malignant lymphomas). An inverse relationship exists between SS-R and receptors for epidermal growth factor (EGF-R) incidence in lung tumors, glial tumors and most breast tumors, whereas meningiomas express simultaneously both receptors. A minority of tumors (ovarian tumors, MTC, insulinomas) express a subtype of SS-R, characterized by low affinity for the octapeptide SS analog octreotide. The function mediated by SS-R in human tumors may differ according to the tumor type. SS-R in pituitary and GEP tumor mediate hormone secretion inhibition with, in addition, possibly some antiproliferative effects. In meningiomas, however, activation of SS-R inhibits forskolin-stimulated adenylate cyclase activity, and weakly stimulates proliferation. Whereas 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 manyfold: (1) as a predictive marker for efficient therapy with octreotide in pituitary and GEP tumors; (2) as a diagnostic marker: for pathobiochemical classification of tumors, using in vitro detection methods; for clinical evaluation using in vivo scanning techniques; (3) as a prognostic marker; and (4) as a potential radiotherapeutic target.
Insights
Somatostatin receptors (SS-R) are found in many tumors, including neuroendocrine and some brain and breast cancers. Their presence can predict treatment response and aid in diagnosis and prognosis.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Somatostatin receptors (SS-R) are expressed in numerous tumor types.
- SS-R are prevalent in neuroendocrine tumors (pituitary, gastroenteropancreatic), paragangliomas, pheochromocytomas, medullary thyroid carcinomas, small cell lung carcinomas, lymphomas, meningiomas, astrocytomas, and breast tumors.
- Tumor differentiation generally correlates with SS-R expression, though exceptions exist.
Purpose of the Study:
- To investigate the presence and function of somatostatin receptors in various human tumors.
- To explore the relationship between SS-R and epidermal growth factor receptors (EGF-R).
- To elucidate the clinical implications of SS-R expression in oncology.
Main Methods:
- Identification of SS-R in membrane homogenates and tissue sections.
- Analysis of SS-R expression patterns in different tumor types.
- Investigation of SS-R functional roles, including hormone secretion inhibition and cell proliferation.
- Assessment of the correlation between SS-R and EGF-R.
Main Results:
- SS-R are widely distributed across various cancers, particularly neuroendocrine tumors.
- An inverse relationship between SS-R and EGF-R was observed in lung, glial, and breast tumors, with co-expression in meningiomas.
- Tumor-specific functions of SS-R were noted, including hormone inhibition and potential antiproliferative effects.
- A subset of tumors exhibits SS-R with low affinity for octreotide.
Conclusions:
- SS-R presence in tumors has significant clinical implications for diagnosis, prognosis, and therapeutic targeting.
- SS-R can serve as predictive markers for therapies like octreotide in specific tumor types.
- Further research is needed to fully understand SS-R-mediated antiproliferative effects in primary human tumors.