Somatostatin receptor subtypes in human thymoma and inhibition of cell proliferation by octreotide in vitro

Somatostatin (SS) and SS receptor (SSR) subtypes, code-named sst(1-5) are heterogeneously expressed in the normal human thymus. This suggests their involvement in controlling the immune and/or neuroendocrine functions in this organ. Moreover, recently a high in vivo uptake of [In-111-DTPA-D-Phe(1)]octreotide has been reported in patients bearing thymoma. The present study characterizes in vivo and in vitro, functional SS-binding sites in a human thymoma. A high uptake of [In-111-DTPA-D-Phe(1)]octreotide was observed in the chest of a patient with myasthenia gravis due to a cortical thymoma. Specific binding of [I-125-Tyr(11)] SS-14 was found on a membrane preparation of the surgically removed thymoma. Scatchard analysis showed high affinity binding sites (K-d, 47.5 +/- 2.5 pmol/L) with low maximum binding capacity (28.5 +/- 2.5 fmol/mg membrane protein). RT-PCR analysis showed the presence of sst(1), sst(2A), and a predominant sst(3) messenger RNA(mRNA) expression in the tumor tissue. Primary cultured tumor cells expressed sst(3) mRNA only. In contrast to the normal thymus, SS mRNA was not expressed. By immunohistochemistry, the tumor cells highly expressed sst, receptors, weakly expressed sst, receptors, and showed no immunostaining for sst, receptors. sst(2A) immunoreactivity was found in the stromal compartment of the tumor, particularly on the endothelium of small intratumoral blood vessels. In primary cultured tumor cells, both SS and octreotide (10 nmol/L) significantly inhibited [H-3]thymidine incorporation by 40.6% and 43.2%, respectively. The following conclusions were reached. 1) As this tumor displayed a high immunoreactivity for sst(3) and the cultured tumor cells expressed the sst, mRNA only, this SSR may be the subtype involved in the inhibition of epithelial tumor cell proliferation by octreotide in vitro. 2) A loss of endogenous SS production in this thymoma might be implicated in the uncontrolled cell growth. 3) In this case, the sst(3) may play a role in determining the uptake of [In-111-DTPA-D-Phe(1)]octreotide by in vivo SS receptor scintigraphy.