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 (sst(1)-sst(5)), the sst(3) receptor displays a distinct pharmacological profile. Like sst(2), the sst(3) receptor efficiently internalizes radiolabeled somatostatin analogs. Unlike sst(2), however, internalized sst(3) receptors are rapidly transferred to lysosomes for degradation. Apart from this, very little is known about the clinical relevance of the sst(3) receptor, which may in part be due to the lack of specific monoclonal sst(3) antibodies.

Methods: Here, we have extensively characterized the novel rabbit monoclonal anti-human sst(3) 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 sst(3) 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 sst(3) 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 sst(3)-expressing tumors during routine histopathological examinations. Given its unique trafficking properties, these tumors may be potential candidates for sst(3)-directed receptor radiotherapy.