Reassessment of sst3 Somatostatin Receptor Expression in Human Normal and Neoplastic Tissues Using the Novel Rabbit Monoclonal Antibody UMB-5

Abstract

Background: Among the five somatostatin receptors (sst₁-sst₅), the sst₃ receptor displays a distinct pharmacological profile. Like sst₂, the sst₃ receptor efficiently internalizes radiolabeled somatostatin analogs. Unlike sst₂, however, internalized sst₃ receptors are rapidly transferred to lysosomes for degradation. Apart from this, very little is known about the clinical relevance of the sst₃ receptor, which may in part be due to the lack of specific monoclonal sst₃ antibodies. Methods: Here, we have extensively characterized the novel rabbit monoclonal anti-human sst₃ antibody UMB-5 using transfected cells and receptor-expressing tissues. UMB-5 was then subjected to immunohistochemical staining of a series of 190 formalin-fixed, paraffin-embedded normal and neoplastic human tissues. Results: Specificity of UMB-5 was demonstrated by detection of a broad band migrating at a molecular weight of 70,000–85,000 in immunoblots from human pituitary. After enzymatic deglycosylation, the size of this band decreased to a molecular weight of 45,000. Tissue immunostaining was completely abolished by pre-adsorption of UMB-5 with its immunizing peptide. In addition, UMB-5 detected distinct cell populations in human tissues like pancreatic islands, anterior pituitary, adrenal cortex, adrenal medulla, and enteric ganglia, similar to that seen with a rabbit polyclonal antibody generated against a different carboxyl-terminal epitope of the sst₃ receptor. In a comparative immunohistochemical study, UMB-5 yielded predominant plasma membrane staining in the majority of pituitary adenomas, pheochromocytomas, and a subset of neuroendocrine tumors. The sst₃ receptor was also present in many glioblastomas, pancreatic, breast, cervix, and ovarian carcinomas. Conclusion: The rabbit monoclonal antibody UMB-5 may prove of great value in the identification of sst₃-expressing tumors during routine histopathological examinations. Given its unique trafficking properties, these tumors may be potential candidates for sst₃-directed receptor radiotherapy.