Pancreatic Somatostatinoma: Abundance of Somatostatin-28(1–2)-Like Immunoreactivity in Tumor and Plasma*

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Abstract
The relative amounts of the different molecular forms of somatostatin-14 like immunoreactivity (S-14 LI) and of somatostatin-28(1-12) like immunoreactivity (S-28(1-12) LI) in extracts of tumor and peripheral plasma of a patient with a pancreatic somatostatinoma were characterized and compared. Tissue and plasma were chromatographed on Sephadex G-50 columns equilibrated with 6 M urea. Immunoreactivity in the eluting fractions was assayed with 2 separate, region specific radioimmunoassays [RIA] using antibodies R149 (S-14 LI) and S309 (S-28(1-12)LI). RIA R149 recognizes the 6-8 and 14 regions of the S-14 sequence and detects S-14, S-28, and prosomatostatin, an .apprx. 14,000 MW precursor for the 2 peptides. RIA S309 recognizes the 2-11 segment of S-28 and reacts with S-28, S-28(1-12), and higher MW S-28(1-12) LI but not S-14. Total tumor S-14 LI was 190 pmol/mg protein and consisted of 3 peaks of immunoreactivity of apparent 14,000 MW (14K S-14 LI), 3200 MW (3.2K corresponding to S-28) and 1600 MW (1.6K corresponding to S-14). The 3 peaks comprised, respectively, 7%, 57%, and 36% of total S-14 LI. Total tumor S-28(1-12) LI was 594 pmol/mg protein and eluted as 4 major peaks of immunoreactivity as follows: peak I MW 15,000, 10% of toal S-28(1-12)LI); peak II MW 8,000, 20% of S-28(1-12) LI), peak III (corresponding to S-28, 19% of S-28(1-12) LI); peak IV (corresponding to S-28(1-12) .apprx. 50% of total S-28(1-12) LI). Total plasma concentration of S-14 LI was 714 pM, being made up of the 3 peaks found in tumor but in the following relative amounts (14K S-14 LI, 22%; 3.2K, 29%; 1.6 K, 49%). Plasma S-28(1-12) LI was 4 times higher (2879 pM) than S-14 LI and contained immunoreactivity corresponding to each of the 4 peaks found in the tumor. The tumor and plasma concentrations of S-28(1-12) LI were greater than that of S-14 LI. Both tumor and plasma S-14 LI and S-28 LI were heterogeneous and comprised species corresponding not only to S-14 but also S-28, S-28(1-12), prosomatostatin, and other higher MW forms of S-28. The finding of high concentration of forms corresponding to S-28(1-12) and 8K S-28(1-12) LI (without S-14 activity) suggests the existence of 2 pathways for synthesis of S-14 from prosomatostatin, either directly (prosomatostatin .fwdarw. S-14 + 8K S-28(1-12) LI) or via S-28 (prosomatostatin .fwdarw. S-28 .fwdarw. S-14 + S-28(1-12). The hormonal effects associated with somatostatinomas must result not only from high circulating levels of S-14 but also from S-28 and higher MW forms with potential biological activity.