Somatostatin (sst) receptors are expressed in many tissues and multiple subtypes are often present in the same cells. Their activation by endogenous sst as well as by sst-analogues leads to inhibition of secretion and growth in some tumor, such as the neuroedocrine ones.
Pheochromocytomas (Pheos) and paragangliomas (PGLs) are neural crest-derived tumors which can be sympathetic or parasympathetic in origin and present themselves as sporadic or familial. Their therapy is surgical but in some cases (metastatic pheos/PGLs or large Head/Neck PGLs) their removal is impossible and an alternative medical therapy is desirable.
We evaluated mRNA expression of the five different sst receptors in 25 Pheo/PGLs obtained at surgery in patients affected by a sporadic (17) or familial (8) tumors. Familial tumors were due to VHL (1), Ret (1), NF-1 (1) and SDHD (5) mutations.
Measurement of sst receptors was performed by quantitative real-time PCR (TaqMan™). Primers and probes for each sst receptors were selected by the proprietary software Primer Express (Applied Biosystem Inc.) Standard curves were made by cloning in PCRRII-TOPO vector (Invitrogen) a specific amplicon for each receptor. Results, expressed as copies/ug total RNA) show similar median values with a wide range of distribution for each receptor class. Median (M) and range (R) values were as following: sst-1: M 3.20E+04; R 7.40E+02 / 2.00E07. sst-2: M 2.56E05; R 1.30E+03 / 9.90E+05. sst-3: M 1.70E+04; R 8.20E+01 / 2.30E+06. sst-4: M 2.68E+04; R 1.40E+03 / 3.10E+05. sst-5: M 5.98E+03; R 4.00E+01 / 1.60E+07.
All the 5 sst receptors subtypes were expressed in the tumors. sst-5 showed the highest variability while sst-2 and sst-4 the lowest. We found no differences among sporadic and familial tumors.
The expression of all the sst receptors subtypes is the first step towards the possible therapeutic use of different sst-analogues in patients with non operable pheos/PGLs.
01 - 05 Apr 2006
European Society of Endocrinology