Somatostatin receptor subtypes in hormone-refractory (castration-resistant) prostatic carcinoma
ABSTRACT The aim of this study was to examine the tissue expression and localisation of the somatostatin receptors (SSTRs) in hormone-refractory (HR) prostate cancer (PCa). Five SSTRs were evaluated immunohistochemically in 20 radical prostatectomies (RPs) with Gleason score (GS) 3+3=6 PCa, in 20 RPs with GS 4+4=8 and 4+5=9 PCa, and 20 transurethral resection of the prostate specimens with HR PCa. The mean values in the cytoplasm (all five SSTRs were expressed), membrane (only SSTR3 and SSTR4 were expressed) and nuclei (only SSTR4 and SSTR5 were expressed) of the glands in HR PCa were 20-70% lower than in the other two groups, the differences being statistically significant. All five SSTRs were expressed in the smooth muscle and endothelial cells of HR PCa, the mean values being lower than in the other two groups. In conclusion, this study expands our knowledge on the expression and localisation of five SSTRs in the various tissue components in the HR PCa compared with hormone-sensitive PCa.
SourceAvailable from: Massimiliano Ruscica[Show abstract] [Hide abstract]
ABSTRACT: The evidence that prostate cancer (PCa) express-es specific receptors for hormones and neuropep-tides, including somatostatin (SRIF) receptors (SSRs) has driven the research towards the identi-fication of new potential diagnostic/therapeutic paths besides the conventional treatment options. Although the first attempts has led to inconclusive results due to the heterogeneity of this tumor and to the complex mechanisms involved in the pro-gression of PCa tumor growth, the potential role of SRIF and its synthetic analogues (SSAs) in the treatment of PCa represents an "open challenge" in the light of the new knowledge about SSR pathophysiology. Indeed, SRIF and SSAs can con-trol tumor cell proliferation by two separate mech-anisms: a direct mechanism through the activa-tion of the five specific SSRs or an indirect mech-anism through the inhibition of secretion of sever-al growth factors and hormones responsible for tumor cell proliferation. Since new SSAs specific for each receptor subtype, as well as bi-specific compounds and panligands have been syn-thetized, the identification of alternative SSR tar-gets on PCa cells and the consequent employment of these new specific molecules in the treatment of advanced PCa (alone or in combination with tra-ditional treatment options), could improve the prognosis particularly of those patients not re-sponding to (anti-) hormonal therapy (hormone-re-fractory PCa patients). KEY WORDS: somatostatin receptors, prostate, can-cer, tumor progression, octreotide, lanreotide.
Pathology 01/2013; 45(1):93-96. DOI:10.1097/PAT.0b013e32835bae76 · 2.62 Impact Factor
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ABSTRACT: Somatostatin (SST) and SST receptors (SS1R, SS2R, SS3R, SS4R and SS5R) appear to play a significant role in the progression of human prostate cancer (PCa), which is associated with heterogeneity of SSRs expression and specific cell localization as we already demonstrated in the LNCaP cell line, an in vitro model of human androgen-dependent PCa. In this study, PC-3 and DU-145 human castration-resistant PCa cells were found to express all SSRs, while LNCaP expressed all but SS4R. A 48-h treatment with BIM-23244 (SS2R/SS5R) or BIM-23926 (SS1R) SST analogs was more effective in inhibiting cell proliferation, compared to BIM-23120 (SS2R), BIM-23206 (SS5R) and BIM-23704 (SS1R/SS2R). BIM-23926 (SS1R) treatment increased the amount of p21 and decreased phosphorylated (p) ERK1/2. BIM-23244 (SS2R/SS5R) led to p21 increment only in PC-3 cells, and to pERK1/2 reduction in both cell lines. SS1R/SS2R and SS2R/SS5R receptor dimers were natively present on cell membrane and their amount was increased by BIM-23704 (SS1R/SS2R) or BIM-23244 (SS2R/SS5R) treatment, respectively. SS1R, SS2R and SS5R were differently distributed among nuclear, lysosomal and microsomal compartment, according to their different recycling dynamics. These results show that, in PC-3, DU-145 and LNCaP cells, activation of SS1R and SS2R/SS5R leads to relevant antiproliferative effects.Molecular and Cellular Endocrinology 11/2013; DOI:10.1016/j.mce.2013.10.027 · 4.24 Impact Factor