Selective activation of somatostatin receptor subtypes differentially modulates secretion and viability in human medullary thyroid carcinoma primary cultures: potential clinical perspectives.
BACKGROUND
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 (SSTR) subtypes 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 secretion as well as cell viability of SRIH analogs interacting with SSTR1, SSTR2, and SSTR5.


METHODS
Thirty-five patients affected by MTC were recruited from 2003 to 2005. After total thyroidectomy, the samples were examined for CT, chromogranin A, 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 tumor 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, whereas cell viability was not affected. On the other hand, in the nonresponder group, CT secretion was reduced by the SSTR1 selective agonist, whereas cell viability was inhibited by SSTR2 selective agonists.


CONCLUSIONS
Our data suggest that SRIH analogs might be useful in medical therapy of MTC because they could have antiproliferative effects despite the lack of antisecretory activity and vice versa.
Zatelli
Maria Chiara
MC
Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy. ti8@unife.it.
Piccin
Daniela
D
Tagliati
Federico
F
Bottoni
Arianna
A
Luchin
Andrea
A
Vignali
Cristina
C
Margutti
Angelo
A
Bondanelli
Marta
M
Pansini
Gian Carlo
GC
Pelizzo
Maria Rosa
MR
Culler
Michael D
MD
Degli Uberti
Ettore C
EC
D000328:Adult; D000368:Aged; D002116:Calcitonin / Q000378:metabolism*; D018276:Carcinoma, Medullary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017481:Receptors, Somatostatin / Q000819:agonists* / Q000032:analysis / Q000145:classification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D053379:Chromogranin A; D002864:Chromogranins; D017481:Receptors, Somatostatin; D002116:Calcitonin