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.
Highlights
Somatostatin is a widely distributed inhibitory peptide hormone that is involved in digestive, endocrine, and immune functions
Analogs, the receptor family can be divided into two subclasses: SST receptors (SSTR)-2,3,5 react with SST octapeptide analogs and constitute members of one subgroup; SSTR-1,4 react poorly with these compounds and fall into another subgroup. [2,4,7,10,11,12,13,14,15]
We aimed to investigate the expression of mRNA for somatostatin receptor subtypes in a cohort of pediatric hematological and oncological specimens using RT-PCR and the binding characteristics of SSTR protein by ligand competition assays
Summary
Somatostatin is a widely distributed inhibitory peptide hormone that is involved in digestive, endocrine, and immune functions. The antiproliferative action of SST and high expression of their corresponding SSTRs on various endocrine tumors led to the clinical application of synthetic stable analogs of SST for hormonal treatment of human malignancies such as acromegaly [2,4,7]. It is reported that octreotide has the highest affinity to SSTR-2, approximately similar affinity to SSTR-5 and SSTR-3, following lower binding affinity to SSTR-1, and displaying the lowest to SSTR-4. Lanreotide shows the highest affinity to SSTR-2 to SSTR-5 and somehow lower binding affinity to SSTR-3 and SSTR-4, and displays the lowest affinity to SSTR-1. Synthetic SST analogs found other useful clinical applications as carrier molecules for radionuclides for tumor visualization and targeted radio- and chemotherapy of SSTR-positive tumors [2,4,7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
