SOMATOSTATIN RECEPTOR SUBTYPE EXPRESSION IN HUMAN THYROID AND THYROID-CARCINOMA CELL-LINES

Somatostatin (SRIH) analogs can suppress the proliferation of human di fferentiated thyroid carcinoma cell lines that express SRIH receptors (SSTRs) demonstrated by radioligand binding analysis. Five distinct hu man SSTR subtypes (hSSTR1-5) that bind native SRIH exhibit diverse aff inities to a wide range of SRIH analogs. Reverse transcriptase-PCR amp lification of ribonucleic acids (RNAs) obtained from normal thyroid ti ssues and nine human thyroid carcinoma cell lines, grown as monolayer cultures and xenograft tumors in nude mice, were used to discriminate expression of SSTR subtype messenger RNAs (mRNAs). The cell lines were derived from a follicular adenoma (KAK-1), two follicular carcinomas (MRO-87 and WRO-82), two papillary carcinomas (NPA87 and KAT-10), and four anaplastic thyroid carcinomas (DRO-90, ARO-81, KAT-4, and KAT-18) . Most thyroid cancer cell line monolayers and xenografts expressed SS TR3 and SSTR5 mRNAs. SSTR1 expression was more varied between monolaye rs and xenografts, whereas SSTR2 mRNA was only faintly detectable at t he most extreme resolution. SSTR4 mRNA was faintly positive in only on e anaplastic carcinoma xenograft. Normal thyroid also expressed SSTR3 and SSTR5 mRNAs, with only faint expression of SSTR1 and SSTR2 mRNAs ( in one of five and three of five samples, respectively). SSTR mRNA exp ression was dependent upon in vitro culture conditions, as xenograft S STR mRNA expression tended to decrease compared to that in each respec tive monolayer culture. Characterization of SSTR subtype expression in human thyroid carcinomas may permit targeting of specific SRIH analog s to inhibit proliferation of differentiated and anaplastic thyroid ca rcinomas in patients.