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  • br Protein level expression of SSTR br Western blots and


    Protein level expression of SSTR1-5
    Western blots and densitometry analysis were used to charac-terize the protein expression of SSTR1-SSTR5 in ATC and FTC cell lines (Fig. 2). All thyroid cancer cell lines expressed SSTR1, SSTR2, SSTR3, and SSTR5 in varying degrees. SSTR3 was highly expressed through all cell lines; Doxorubicin however, none of the Doxorubicin analyzed ex-pressed SSTR4 at a protein level.
    Fig. 1. mRNA expression of somatostatin receptors (SSTR1-SSTR5) varies between FTC and ATC cell lines. SSTR1 (A) is only expressed by FTC-236. SSTR2 (B), SSTR3 (C) and SSTR5 (D) are variably expressed by all cell lines.
    Fig. 2. Densitometry analysis was carried by normalizing target protein expression to betaactin levels. SSTR3 showed the highest expression of all SSTRs followed by SSTR1
    Antiproliferative effect of OCT, SOM230, and KE-108 in ATC and FTC cell lines
    Human tissue microarrays
    Tissue samples were formalin-fixed, para n-embedded, core thyroid biopsies mounted in triplicate (Fig. 4). The Vectra plat-form was employed to acquire images and measure SSTR2 staining intensities within the nuclear and cytoplasmic segments of each core. SSTR2 was absent in 10 normal thyroid tissues but present in 3 aggressive human thyroid cancers.
    There is an existing clinical challenge for the treatment of ag-gressive thyroid cancers, such as metastatic FTC and ATC.1,14 FTC and ATC represent 19% and 1%–2% of all thyroid cancers, respec-tively. Coupling the poor differentiation of ATC with its frequent metastasis, however, accounts for over half of thyroid cancer– related deaths.15,16 All patients with ATC are classified as having
    Fig. 4. SSTR2 was strongly expressed on (A) poorly differentiated thyroid cancer tissue and moderately expressed on a (B) PTC thyroid cancer tissue. No SSTR2 expression was found on normal thyroid samples.
    a stage IV disease. Although most well-differentiated thyroid can-cers can be cured via thyroidectomy and radioactive iodine abla-tion, approximately 20% of patients present a more aggressive phe-notype with distant metastasis or recurrence associated with in-creased mortality.17,18 Therefore, there exists a pressing need for alternative therapies for aggressive thyroid cancers.
    Thyroid tumors are known to express SSTRs distinctively de-pending on whether they are medullary thyroid cancer or the non-medullary tumors, PTC, FTC, or ATC.7,8 Current literature, however, suggests conflictive data on SSTR expression for the aggressive thy-roid cancers ATC and metastatic FTC.
    In an effort to unite these conflicting views, our study demon-strated that ATC and FTC cell lines expressed SSTR1, SSTR2, SSTR3, and SSTR5 in varying degrees. SSTR3 was highly expressed through all cell lines, followed by SSTR1, SSTR2, and SSTR5. None of the cells analyzed expressed SSTR4 at a protein or message level. Moreover, we found that there is a clear correlation between mRNA and protein expression for SSTR3, SSTR2, and SSTR5. We fur-ther attest the presence of a varied expression of SSTRs via the use of SST analogs OCT, KE-108, and SOM230. KE-108, a pansomato-statin receptor agonist, SSTR1–SSTR5, and pasireotride (SOM230), an SSTR5, SSTR3>>SSTR2 agonist, exhibited the best antiprolif-erative activity among these de-differentiated thyroid cancer cell lines. These results suggest that SST analogs could indeed be uti-lized as therapeutic agents for aggressive thyroid cancers. Although OCT was seemingly ineffective in our thyroid cancer cell lines, we cannot rule out its potential therapeutic e cacy against aggressive thyroid cancers given that our human thyroid tissues had substan-tial SSTR2 expression.
    In conclusion, our results suggest that somatostatin receptor subtypes (SSTR1–SSTR3 and SSSTR5) are pertinent and potentially promising therapeutic targets for aggressive thyroid cancers. Our study is limited by the scarcity of both ATC and FTC cell lines as well as human thyroid samples of ATC and FTC. Further stud-ies should look to characterize the role of SSTRs and somato-statin analogues on these aggressive thyroid cancers, for instance, to continue working on TMAs to further characterize expression