Context: Medullary thyroid carcinoma (MTC) is a rare tumor originating from thyroid parafollicular C cells. We previously demonstrated that somatostatin (SRIH) reduces cell growth in the human MTC cell line, TT, which expresses all SRIH receptor subtypes (SSTR) and responds differently to selective SSTR agonists.

Objective: To clarify the possible effects of SRIH analogs on hormone secretion and proliferation in MTC primary cultures, we evaluated SSTR expression and assessed the in vitro effects on calcitonin (CT) and Chromogranin A (CgA) secretion, as well as on cell viability of SRIH analogs interacting with SSTR1, SSTR2 and SSTR5.

Design: Thirty-five patients affected from MTC were recruited from 2003 to 2005. After total thyroidectomy, the samples were examined for CT, CgA and SSTR expression by RT-PCR. Primary cultures were developed and tested with SRIH analogs interacting with SSTR1, SSTR2 and SSTR5.

Results: We selected 18 MTC tumors samples, expressing SSTR1, SSTR2 and SSTR5. Two different groups were identified according to CT secretion inhibition by the clinically available SRIH analog, lanreotide. In the "responder" group, CT secretion was reduced by compounds interacting with SSTR1, SSTR2 and SSTR5, while cell viability was not affected. On the other hand, in the "non responder" group, CT secretion was reduced by the SSTR1 selective agonist, while cell viability was inhibited by SSTR2 selective agonists.

Conclusions: Our data suggest that SRIH analogs might be useful in medical therapy of MTC, since they could have antiproliferative effects despite the lack of antisecretory activity, and vice versa.