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[Somatostatin receptors in non-endocrine tumours]
C Casini Raggi1, P Pinzani, S Gelmini
1Unità di Endocrinologia, Università degli Studi, Florence, Italy.
Abstract:
The study of the antiproliferative action of somatostatin (ss) is important not only to understand the regulation of neuroendocrine tumours that express receptors (sst), but also non-endocrine tumours which express these receptors. We previously demonstrated the presence of sst2 in a wide panel of cell lines from human neuroblastoma. Although hypotheses have been put forward that treatment with ss or its analogs may be beneficial in oncological patients, this does not appear to be the case in neuroblastoma; patients with high sst2 levels (who are therefore sensitive to ss treatment) have per se a relatively positive outcome. Therefore, adjuvant treatment with ss is not necessary. Viceversa, patients with a poor prognosis are essentially characterized by a low expression of sst2 (and therefore are insensitive to a therapy with ss). In these patients adjuvant treatment with ss might be indicated, but would have little chance of success. Although the majority of neuroendocrine tumours expresses sst2, pancreas and prostate cancer express sst1 but not sst2, and are therefore insensitive to octreotide treatment which binds preferentially to sst2. Tumours like colorectal carcinoma and breast cancer also express sst2 in their more favourable forms. However, the concentration of sst2 in colorectal cancer is similar, if not lower than that in the surrounding normal tissue. Therefore, the probability of successful adjuvant therapy with ss is relatively low. In breast cancer, it is possible that sensitivity to estrogens may have a positive influence on the expression of sst2. This might justify clinical trials with ss in breast cancer.
Insights
Somatostatin (ss) treatment is not beneficial for neuroblastoma patients with high sst2 levels. Low sst2 expression in poor-prognosis neuroblastoma indicates limited success for ss therapy.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Somatostatin receptors (sst) are expressed in various tumors, influencing treatment strategies.
- Neuroblastoma and other cancers express somatostatin receptors, prompting investigation into somatostatin (ss) as a therapeutic agent.
Purpose of the Study:
- To evaluate the antiproliferative action of somatostatin (ss) in neuroendocrine and non-endocrine tumors.
- To determine the clinical utility of ss therapy based on somatostatin receptor (sst) expression levels in various cancers, including neuroblastoma, pancreatic cancer, prostate cancer, colorectal carcinoma, and breast cancer.
Main Methods:
- Analysis of sst2 expression in human neuroblastoma cell lines.
- Correlation of sst2 levels with patient prognosis and sensitivity to ss treatment.
- Review of sst receptor expression patterns in pancreatic, prostate, colorectal, and breast cancers.
Main Results:
- High sst2 levels in neuroblastoma correlate with a positive outcome, rendering adjuvant ss therapy unnecessary.
- Low sst2 expression in poor-prognosis neuroblastoma suggests limited efficacy of ss therapy.
- Pancreatic and prostate cancers express sst1 but not sst2, making them insensitive to octreotide.
- Colorectal and breast cancers express sst2, but concentrations are similar to normal tissue, indicating low probability of successful ss therapy.
- Estrogen sensitivity may positively influence sst2 expression in breast cancer.
Conclusions:
- Adjuvant somatostatin (ss) therapy is not indicated for neuroblastoma patients with high sst2 expression.
- The efficacy of ss therapy is limited in cancers with low sst2 expression, such as poor-prognosis neuroblastoma.
- Further clinical trials with ss are warranted for breast cancer, given the potential influence of estrogen on sst2 expression.