Somatostatin receptor subtypes in human thymoma and inhibition of cell proliferation by octreotide in vitro.
Somatostatin (SS) and SS receptor (SSR) subtypes, code-named sst1-5, 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 [111In-DTPA-D-Phe1]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 [111In-DTPA-D-Phe1]octreotide was observed in the chest of a patient with myasthenia gravis due to a cortical thymoma. Specific binding of [125I-Tyr11] SS-14 was found on a membrane preparation of the surgically removed thymoma. Scatchard analysis showed high affinity binding sites (Kd, 47.5 +/- 2.5 pmol/L) with low maximum binding capacity (23.5 +/- 2.5 fmol/mg membrane protein). RT-PCR analysis showed the presence of sst1, sst2A, and a predominant sst3 messenger RNA (mRNA) expression in the tumor tissue. Primary cultured tumor cells expressed sst3 mRNA only. In contrast to the normal thymus, SS mRNA was not expressed. By immunohistochemistry, the tumor cells highly expressed sst3 receptors, weakly expressed sst1 receptors, and showed no immunostaining for sst2A receptors. sst2A 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 [3H]thymidine incorporation by 40.6% and 43.2%, respectively. The following conclusions were reached. 1) As this tumor displayed a high immunoreactivity for sst3 and the cultured tumor cells expressed the sst3 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 sst3 may play a role in determining the uptake of [111In-DTPA-D-Phe1]octreotide by in vivo SS receptor scintigraphy.
Ferone
D
D
Department of Internal Medicine III, Erasmus University, Rotterdam, The Netherlands.
van Hagen
M P
MP
Kwekkeboom
D J
DJ
van Koetsveld
P M
PM
Mooy
D M
DM
Lichtenauer-Kaligis
E
E
Schönbrunn
A
A
Colao
A
A
Lamberts
S W
SW
Hofland
L J
LJ
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007205:Indium Radioisotopes; D008875:Middle Aged; D015282:Octreotide / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011877:Radionuclide Imaging; D017481:Receptors, Somatostatin / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000235:genetics / Q000494:pharmacology; D013945:Thymoma / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000473:pathology; D013953:Thymus Neoplasms / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000473:pathology; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D007205:Indium Radioisotopes; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C071632:SDZ 215-811; D013004:Somatostatin; D004369:Pentetic Acid; D015282:Octreotide