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. 2020 Dec 7;25(23):5775.
doi: 10.3390/molecules25235775.

Expression of Somatostatin Receptor Subtypes (SSTR-1-SSTR-5) in Pediatric Hematological and Oncological Disorders

Kristof Harda  1   2 , Zsuzsanna Szabo  1 , Eva Juhasz  3 , Balazs Dezso  4 , Csongor Kiss  3 , Andrew V Schally  5   6   7   8 , Gabor Halmos  1   5
Affiliations

Expression of Somatostatin Receptor Subtypes (SSTR-1-SSTR-5) in Pediatric Hematological and Oncological Disorders

Kristof Harda et al. Molecules. .

Abstract

Hematological and oncological disorders represent leading causes of childhood mortality. Neuropeptide somatostatin (SST) has been previously demonstrated in various pediatric tumors, but limited information exists on the expression and characteristics of SST receptors (SSTR) in hematological and oncological disorders of children. We aimed to investigate the expression of mRNA for SSTR subtypes (SSTR-1-5) in 15 pediatric hematological/oncological specimens by RT-PCR. The presence and binding characteristics of SSTRs were further studies by ligand competition assay. Our results show that the pediatric tumor samples highly expressed mRNA for the five SSTR subtypes with various patterns. The mRNA for SSTR-2 was detected in all specimens independently of their histological type. A Hodgkin lymphoma sample co-expressed mRNA for all five SSTR subtypes. SSTR-3 and SSTR-5 were detected only in malignant specimens, such as rhabdomyosarcoma, Hodgkin lymphoma, acute lymphoblastic leukemia, and a single nonmalignant condition, hereditary spherocytosis. The incidence of SSTR-1 and SSTR-4 was similar (60%) in the 15 specimens investigated. Radioligand binding studies demonstrated the presence of specific SSTRs and high affinity binding of SST analogs in pediatric solid tumors investigated. The high incidence of SSTRs in hematological and oncological disorders in children supports the merit of further investigation of SSTRs as molecular targets for diagnosis and therapy.

Keywords: hematological-oncological disorders in children; somatostatin analogs; somatostatin receptors.

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Conflict of interest statement

The authors declare no conflict of interests in this work. The founding sponsors had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Representative RT-PCR analysis of mRNA for somatostatin receptor (SSTR) subtypes (SSTR-1–5) in one representative pediatric Hodgkin lymphoma specimen. M: DNA marker 50 bp; P: Positive control (human bladder carcinoma); N: Negative template control; T: Pediatric tumor specimen (patient number 4, Hodgkin lymphoma) positive for all 5 SSTR subtypes (SSTR-1–5).
Figure 2
Figure 2
A representative figure of the expression of β-actin housekeeping gene in pediatric hematological and oncological specimens. M: DNA marker (50 bp); P: positive control (human pituitary); N: negative template control; 1–3: Representative pediatric samples.
Figure 3
Figure 3
Representative displacement of [125I]RC-160 binding to membrane fractions of human rhabdomyosarcoma specimen by increasing concentrations of somatostatin (SST) analog RC-160 (Vapreotide) (●), cytotoxic SST analog AN-162 (▼) and RC-121, carrier peptide of AN-162 (○). Other unrelated peptides like LHRH, GHRH, VIP, bombesin, and epidermal growth factor (∇) did not displace the radioligand. Each point represents mean of duplicate or triplicate determinations.
Figure 4
Figure 4
SSTR-based potential downstream pathways and signaling cascades leading to the modulation of hormone secretion, cell growth, and apoptosis. (based on references [10,11,12,15,37] with modifications).
See this image and copyright information in PMC

References

    1. Drastikova M., Beranek M., Gabalec F., Netuka D., Masopust V., Cesak T., Marek J., Palicka V., Cap J. Expression profiles of somatostatin, dopamine, and estrogen receptors in pituitary adenomas determined by means of synthetic multilocus calibrators. Biomed. Pap. 2016;160:238–243. doi: 10.5507/bp.2015.058. - DOI - PubMed
    1. Reubi J.C., Laissue J., Krenning E., Lamberts S.W. Somatostatin receptors in human cancer: Incidence, characteristics, functional correlates and clinical implications. J. Steroid Biochem. Mol. Biol. 1992;43:27–35. doi: 10.1016/0960-0760(92)90184-K. - DOI - PubMed
    1. Cakir M., Dworakowska D., Grossman A. Somatostatin receptor biology in neuroendocrine and pituitary tumours: Part 2—Clinical implications. J. Cell. Mol. Med. 2010;14:2585–2591. doi: 10.1111/j.1582-4934.2010.01125_1.x. - DOI - PMC - PubMed
    1. Schally A.V., Halmos G. Drug Delivery in Oncology. Wiley-VCH Verlag GmbH & Co. KGaA; Weinheim, Germany: 2012. Targeting to peptide receptors; pp. 1219–1261.
    1. Harda K., Szabo Z., Szabo E., Olah G., Fodor K., Szasz C., Mehes G., Schally A.V., Halmos G. Somatostatin receptors as molecular targets in human uveal melanoma. Molecules. 2018;23:1535. doi: 10.3390/molecules23071535. - DOI - PMC - PubMed

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