Somatostatin receptor gene expression in neuroblastoma

Somatostatin receptor expression is a favorable prognostic factor in human neuroblastoma. Somatostatin receptors have been demonstrated in vitro by pharmacologic analysis of tumor tissue and in vivo by diagnostic radioreceptor scintigraphy. However, which receptor subtypes ( sst 1, sst 2, sst 3, sst...

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Published in:Regulatory peptides 2000-03, Vol.88 (1), p.61-73
Main Authors: Albers, Anne R, O’Dorisio, M.Sue, Balster, Douglas A, Caprara, Moonkyung, Gosh, Pradip, Chen, Feng, Hoeger, Carl, Rivier, Jean, Wenger, Gail D, O’Dorisio, Thomas M, Qualman, Stephen J
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Transplantation
Child
Child, Preschool
COS Cells
Female
Gene Expression
Humans
Infant
Infant, Newborn
Male
Medical sciences
Membrane Proteins
Mice
Mice, Nude
Neuroblastoma
Neuroblastoma - genetics
Neuroblastoma - pathology
Neurology
Receptors, Somatostatin - genetics
Somatostatin receptors
Transplantation, Heterologous
Tumor Cells, Cultured
Tumors of the nervous system. Phacomatoses
Xenograft tumors
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Summary:Somatostatin receptor expression is a favorable prognostic factor in human neuroblastoma. Somatostatin receptors have been demonstrated in vitro by pharmacologic analysis of tumor tissue and in vivo by diagnostic radioreceptor scintigraphy. However, which receptor subtypes ( sst 1, sst 2, sst 3, sst 4, and sst 5) are expressed in these tumors has not yet been delineated. We used RT-PCR to analyze expression of the five somatostatin receptor genes in 32 neuroblastoma tumor specimens. All 32 tumor specimens expressed mRNA for c-abl and sst 1; sst 2 mRNA was detected in 27/32 samples and somatostatin mRNA was detected in 30/32 tumor specimens. The remaining receptor subtypes, sst 3, sst 4, and sst 5 were variably expressed. Receptor protein for sst 1 and sst 2 was visualized in tumor neuroblasts as well as in endothelial cells of tumor vessels using immunostaining with specific anti-receptor antibodies. The effect of high expression of somatostatin receptors on cell proliferation was examined in SKNSH neuroblastoma cells transfected with sst 1 and sst 2. SS 14 binding to wild-type SKNSH cells was undetectable; but the native peptide bound with high affinity to the SKNSH/ sst 1 and SKNSH/ sst 2 neuroblastoma cell lines. Pharmacologic analysis of binding with two long-acting analogues, CH275 and octreotide, confirmed selective expression of sst 1 and sst 2 in stably transfected SKNSH cells. Formation of neuroblastoma xenograft tumors in nude mice was significantly delayed for both SKNSH/ sst 1 ( P
ISSN:0167-0115
1873-1686
DOI:10.1016/S0167-0115(99)00121-4