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 h eterogeneously expressed in the normal human thymus. This suggests their in volvement 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)]o ctreotide 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 bi nding of [I-125-Tyr(11)] SS-14 was found on a membrane preparation of the s urgically 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 th e tumor tissue. Primary cultured tumor cells expressed sst(3) mRNA only. In contrast to the normal thymus, SS mRNA was not expressed. By immunohistoch emistry, the tumor cells highly expressed sst, receptors, weakly expressed sst, receptors, and showed no immunostaining for sst, receptors. sst(2A) im munoreactivity was found in the stromal compartment of the tumor, particula rly on the endothelium of small intratumoral blood vessels. In primary cult ured tumor cells, both SS and octreotide (10 nmol/L) significantly inhibite d [H-3]thymidine incorporation by 40.6% and 43.2%, respectively. The following conclusions were reached. 1) As this tumor displayed a high i mmunoreactivity for sst(3) and the cultured tumor cells expressed the sst, mRNA only, this SSR may be the subtype involved in the inhibition of epithe lial tumor cell proliferation by octreotide in vitro. 2) A loss of endogeno us SS production in this thymoma might be implicated in the uncontrolled ce ll growth. 3) In this case, the sst(3) may play a role in determining the u ptake of [In-111-DTPA-D-Phe(1)]octreotide by in vivo SS receptor scintigrap hy.