Somatostatin receptor subtype mRNA expression in human colorectal cancer and normal colonic mucosae

Laws, Siobhan; Gough, A C; Evans, Angharad; Bains, M. A.; Primrose, John

doi:10.1038/bjc.1997.59

Cited by 37 publications

(24 citation statements)

References 25 publications

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“…Kimura et al also reported that crypt cells of mucosa of GI tract were positive for sstr2A [32]. Laws et al [33] and Raggi et al [6] reported the presence of sstr2 and sstr5 and Hope et al [34] also reported sstr1 in colonic mucosa using RT-PCR. In our present study, both colonic and rectal mucosa demonstrated not only sstr2A immunoreactivity but also sstr1, 2B and 5 in the great majority of crypt cells of GI tract.…”

Section: Discussionmentioning

confidence: 99%

Systemic Distribution of Somatostatin Receptor Subtypes in Human: An Immunohistochemical Study

et al. 2005

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Abstract. Somatostatin is well known to inhibit the hormone secretion of various peptides. This action has been considered to be generally mediated via six different specific somatostatin receptors (sstr), sstr1, sstr2A, sstr2B, sstr3, sstr4, and sstr5. It then becomes very important to demonstrate the localization of these sstr subtypes in order to elucidate the possible biological and/or clinical significance of somatostatin actions. These sstr subtypes have been demonstrated to be expressed throughout the human body, including the central nervous system, gastrointestinal tract, pancreas, kidney, and other organs, but its details, especially its systemic distribution and localization in tissue compartments, have yet to be examined thoroughly in human. Therefore, in this study, we examined the systemic localization of all six somatostatin receptors in normal human organs using immunohistochemistry with recently developed specific antibodies against these receptor subtypes. In all of the human tissues examined, various sstr subtypes were detected not only in parenchymal cells but also in various stromal cells such as lymphocytes, fibroblasts, and endothelial cells. Among human tissues in which the presence of sstr has not been previously reported, the parotid gland demonstrated immunoreactivity for sstr2B and sstr5, bronchial gland for sstr1, 2B, 3, 4, 5, parathyroid gland for sstr1, 3, 4, and duodenum for all subtypes immunoreactivity. The great majority of other organs examined demonstrated results consistent with those of previously reported biochemical studies. In pancreatic islet cells, only sstr2A was positive in all the cases but other sstr subtypes were associated with marked intraislet heterogeneity in their distribution. In stomach, all subtypes of receptor were detected in various cell types of the mucosa, but none in ECL cells of fundic gland. These findings demonstrated the broad systemic actions of somatostatin in non-endocrine cells.

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Section: Discussionmentioning

confidence: 99%

Systemic Distribution of Somatostatin Receptor Subtypes in Human: An Immunohistochemical Study

et al. 2005

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“…Previously, Buscail et al (13) have shown that hsst2 frequency of expression decreased with the tumor stage (3/6, 1/5, or 0/3 in Duke's stages B, C, and D respectively). Using RT-PCR and in situ hybridization, Laws et al (14) have found that hsst2 mRNA was widely distributed in normal mucosa and stroma in 90% of samples. We found that hsst2 mRNA was expressed at a high frequency throughout all tumor stages without any decrease of expression in advanced stage tumors.…”

Section: Discussionmentioning

confidence: 99%

No loss of sst receptors gene expression in advanced stages of colorectal cancer

Vuaroqueaux¹,

Dutour²,

Briard³

et al. 1999

European Journal of Endocrinology

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As demonstrated by several studies, the pan-inhibitory peptide somatostatin (SS) is implicated in a large variety of physiological processes in the gastrointestinal tractus. SS inhibits hormonal and gastric acid secretions, and decreases gastric and intestinal motility, mesenteric blood flow and intestinal absorption. In vitro and in vivo studies showed also that the antiproliferative potency of SS analogs may be a target to improve the prognosis of colorectal cancer. Here we report the expression profile of the five SS receptor subtypes (hsst1-5) mRNAs in a large set of tumoral and normal colon. Using reverse transcription-PCR, we showed that hsst5, hsst1 and hsst2 mRNA subtypes were the most frequently expressed hsst mRNA subtypes in normal and pathological colon. Interestingly, we found that the frequency of hsst5 mRNA expression in the left colon was significantly higher in tumors than in normal samples: 81.2% (13/16) and 36.4% (4/11) respectively (0.025 > P > 0.01, x 2 test with Yates' correction). We did not find any influence of Dukes' stage on hsst mRNAs expression. Of interest, no loss of hsst2 and hsst5 mRNA expression in advanced stages was noted. Some differences in the frequency of expression of hsst mRNAs according to the origin of the tissue (left or right colon) were evident. The expression of hsst5 and hsst2 mRNA in advanced colorectal carcinoma associated with the development of new SS analogs boost the relevance of colorectal cancer treatment by somatostatin analogs.

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“…More recently, cloning of 5 hSSTR has enabled the expression of individual somatostatin receptor expressions to be determined using techniques such as in situ hybridization, RNA-ase protection and reverse transcriptase polymerase chain reactions (RT-PCR) [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. Studies using these techniques indicate that there is considerable heterogeneity between and within individual tumors with respect to the density of the individual hSSTRs expressed.…”

Section: Expression and Functional Role Of Somatostatin Receptors In mentioning

confidence: 99%

Somatostatin Analogs in Oncology: A Look to the Future

Jenkins

Kynaston²,

Davies³

et al. 2001

Chemotherapy

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In the past 15 years considerable advances have been made in our understanding of the molecular pharmacology of the mechanisms whereby somatostatin and its analogs mediate their direct and indirect antineoplastic effects. However, some important issues remain to be resolved, in particular the functional roles of the individual somatostatin receptors (SSTR-1–5) in tumor tissue and up- or downregulation of the hSSTRs with prolonged administration of somatostatin analogs. Answers to these questions are essential before we can maximize the therapeutic efficacy of somatostatin analogs in cancer. For example, is continuous administration more or less effective than intermittent therapy? The role of somatostatin analogs in the management of acromegaly and to a lesser extent neuroendocrine tumors is firmly established. The development of depot preparations of all 3 somatostatin analogs currently available for clinical use will undoubtedly improve both patient compliance and quality of life in patients with these conditions. There are only likely to be minor differences in the therapeutic efficacy of octreotide, lanreotide and vapreotide since all three analogs exert the majority of their antineoplastic effects via hSSTR-2 and hSSTR-5 and at the end of the day, price may well dictate which of these drugs oncologists use to provide symptomatic palliation of acromegaly and neuroendocrine tumors. Apart from some notable exceptions, somatostatin analog therapy has proven to be very disappointing in the management of advanced malignancy. Improvements in the management of solid tumors are likely to come only from combination therapy of somatostatin analogs with cytotoxic agents or other hormones in both advanced malignancy and in the adjuvant setting. Clinical trials with clear-cut objective outcome measures and health-related quality of life assessment are needed to evaluate the therapeutic efficacy of combination treatment in advanced malignancy and as an adjuvant to surgery. Particular attention needs to be paid to possible adverse effects of somatostatin analog therapy on the immune response to cancer. Further studies are required to establish whether the adverse effects of somatostatin analog therapy alone or in combination with cytotoxics or other hormones can be reversed with appropriate immunomodulatory treatment. Targeted somatostatin analog radiotherapy and chemotherapy are currently being investigated and the results of these studies are awaited with interest. Novel approaches using combinations of somatostatin analogs with antiangiogenic drugs or gene therapy are of particular interest and may provide important advances in the management of cancer in the not too distant future.

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Somatostatin receptor subtype mRNA expression in human colorectal cancer and normal colonic mucosae

Cited by 37 publications

References 25 publications

Systemic Distribution of Somatostatin Receptor Subtypes in Human: An Immunohistochemical Study

Systemic Distribution of Somatostatin Receptor Subtypes in Human: An Immunohistochemical Study

No loss of sst receptors gene expression in advanced stages of colorectal cancer

Somatostatin Analogs in Oncology: A Look to the Future

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