Prognostic role of somatostatin receptor subtypes in human prostate cancer

e16120 Background: Neuroendocrine differentiation (NED) in prostate carcinoma (PC) is frequently detected by immunohistochemistry as single cells in conventional adenocarcinoma. NED of PC correlates with poor prognosis and tumor progression during androgen-deprivation therapy. The aim of our study was to correlate the expression of somatostatin receptor (SSTR) 1, 2, 3, 4, 5 subtypes in primary PC with NED pattern and Overall Survival (OS). Methods. PC tissues were reviewed from 100 pts who had undergone biopsy or radical prostatectomy for previously untreated advanced or metastatic PC from 2002 to 2007. 24 samples expressed hystologically chromogranin A (CgA), a marker of NED expression. Patient characteristics included: median age 68 years (range 45–83), median baseline PSA: 70 ng/ml (range 0.3–200), median ECOG Performance Status: 1 (range 0–2), Gleason score ≥ 7, medium serum level of CgA was 56.2 nmol/L (range 0.5–120). Results: The expression of SSTR subtypes (1, 2, 3, 4, 5) were investigated and our data identified four histological features. SSTR1 was expressed in 4/24 samples, SSTR 5 was detected in 2/24 samples, both SSTR1 and SSTR5 were found in 6/24 samples. OS at last follow up on July 2008 was 60%. SSTR 1–5 were undetectable in 12/24 pts with more aggressive clinical course and the OS was < 10%. The PSA and CgA levels were not correlated with clinical outcome. SSTR subtypes 2, 3 an 4 were not expressed in all 24 samples. Conclusions: SSTRs expression significantly correlated with OS. The absence of SSTR 1 and 5 in more aggressive disease could represent a growth advantage in NED prostate cancer. SSTRs and somatostatin analogs are potential targets for prostate cancer treatment. No significant financial relationships to disclose.

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Immunohistochemical Expression and Localization of Somatostatin Receptor Subtypes in Prostate Cancer with Neuroendocrine Differentiation

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463201002300213 ◽

2010 ◽

Vol 23 (2) ◽

pp. 511-522 ◽

Cited By ~ 7

Author(s):

D. Morichetti ◽

R. Mazzucchelli ◽

A. Santinelli ◽

D. Stramazzotti ◽

A. Lopez-Beltran ◽

...

Keyword(s):

Prostate Cancer ◽

Somatostatin Receptor ◽

Neuroendocrine Differentiation ◽

Receptor Subtypes ◽

Immunohistochemical Expression ◽

Somatostatin Receptor Subtypes

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Expression of somatostatin receptor subtypes, aurora kinase A, and interleukin-6 in prostate cancer before androgen ablation.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.e564 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. e564-e564

Author(s):

Angela Gernone ◽

Senia Trabucco ◽

Leonardo Resta ◽

Anna Napoli

Keyword(s):

Prostate Cancer ◽

Interleukin 6 ◽

Single Cells ◽

Somatostatin Receptor ◽

Somatostatin Analogs ◽

Aurora Kinase ◽

Receptor Subtypes ◽

Aurora Kinase A ◽

Androgen Ablation ◽

Kinase A

e564 Background: Neuroendocrine differentiation (NED) in prostate cancer (PC) can be detected by immunohistochemistry as single cells in conventional adenocarcinoma. The extent of NED is associated with poor prognosis and early onset of castrate resistant prostate cancer. Aurora kinase A (AURKA) and Interleukin-6 (IL-6) cooperate to induce NED. The aim of this study was to correlate the expression of somatostatin receptor (SSTR) 1- 2- 3- 4- 5 subtypes, AURKA and IL-6 in primary PC with NED pattern and OS. Methods: PC tissues were reviewed from 60 pts who had undergone biopsy or radical prostatectomy for previously untreated advanced or metastatic PC from 2010 to 2016. 10 samples expressed histologically chromogranin A (CgA), a marker of NED expression. Median age was 67 years (47-80), Gleason score ≥ 7, median PSA was 60 ng/ml (1.3-1000), ECOG 0/1 and bone-visceral sites measurable in 90% of cases. For comparison purposes, 8 pathology specimens from pts with primary PC were used. Results: SSTR1-2-4-5 were detected in the nucleus of PC cells in 10/10 samples. SSTR3 and AURKA were not expressed in all 10 samples. IL-6 was detected in 9/10 samples. All 10 pts were associated with a more aggressive clinical course and OS was < 12 mos. Conclusions: In metastatic prostate cancer, pretreatment NED pattern can be a predictor for progression and survival after hormonal and chemotherapy. SSTRs and somatostatin analogs are not potential targets for prostate cancer.

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Evaluation of a New 177Lu-Labeled Somatostatin Analog for the Treatment of Tumors Expressing Somatostatin Receptor Subtypes 2 and 5

Molecules ◽

10.3390/molecules25184155 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4155

Author(s):

Rosalba Mansi ◽

Guillaume Pierre Nicolas ◽

Luigi Del Pozzo ◽

Karim Alexandre Abid ◽

Eric Grouzmann ◽

...

Keyword(s):

Somatostatin Receptor ◽

Somatostatin Analogs ◽

Somatostatin Analog ◽

Receptor Subtypes ◽

In Vivo Evaluation ◽

Somatostatin Receptor Subtypes ◽

Lower Extent ◽

Lower Background

Targeted radionuclide therapy of somatostatin receptor (SST)-expressing tumors is only partially addressed by the established somatostatin analogs having an affinity for the SST subtype 2 (SST2). Aiming to target a broader spectrum of tumors, we evaluated the bis-iodo-substituted somatostatin analog ST8950 ((4-amino-3-iodo)-d-Phe-c[Cys-(3-iodo)-Tyr-d-Trp-Lys-Val-Cys]-Thr-NH2), having subnanomolar affinity for SST2 and SST5, labeled with [177Lu]Lu3+ via the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). Human Embryonic Kidney (HEK) cells stably transfected with the human SST2 (HEK-SST2) and SST5 (HEK-SST5) were used for in vitro and in vivo evaluation on a dual SST2- and SST5-expressing xenografted mouse model. natLu-DOTA-ST8950 showed nanomolar affinity for both subtypes (IC50 (95% confidence interval): 0.37 (0.22–0.65) nM for SST2 and 3.4 (2.3–5.2) for SST5). The biodistribution of [177Lu]Lu-DOTA-ST8950 was influenced by the injected mass, with 100 pmol demonstrating lower background activity than 10 pmol. [177Lu]Lu-DOTA-ST8950 reached its maximal uptake on SST2- and SST5-tumors at 1 h p.i. (14.17 ± 1.78 and 1.78 ± 0.35%IA/g, respectively), remaining unchanged 4 h p.i., with a mean residence time of 8.6 and 0.79 h, respectively. Overall, [177Lu]Lu-DOTA-ST8950 targets SST2-, SST5-expressing tumors in vivo to a lower extent, and has an effective dose similar to clinically used radiolabeled somatostatin analogs. Its main drawbacks are the low uptake in SST5-tumors and the persistent kidney uptake.

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Novel insights in somatostatin receptor physiology

Acta Endocrinologica ◽

10.1530/eje.1.02354 ◽

2007 ◽

Vol 156 (suppl_1) ◽

pp. S3-S11 ◽

Cited By ~ 42

Author(s):

Giovanni Tulipano ◽

Stefan Schulz

Keyword(s):

Somatostatin Receptor ◽

Somatostatin Receptors ◽

Somatostatin Analogs ◽

Receptor Subtypes ◽

Ligand Complex ◽

Endosomal Sorting ◽

Intracellular Vesicle ◽

Molecular Events ◽

Somatostatin Receptor Subtypes

The experimental data reviewed in the present paper deal with the molecular events underlying the agonist-dependent regulation of the distinct somatostatin receptor subtypes and may suggest important clues about the clinical use of somatostatin analogs with different pattern of receptor specificity for the in vivo targeting of tumoral somatostatin receptors. Somatostatin receptor subtypes are characterized by differential β-arrestin trafficking and endosomal sorting upon agonist binding due, at least in part, to the differences in their C-terminal tails. Moreover, the subcellular expression pattern of somatostatin receptor subtypes and their activity in response to agonist treatment are affected by intracellular complements, such as proteins involved in intracellular vesicle trafficking. Different somatostatin analogs may induce distinct conformations of the receptor/ligand complex, preferentially coupled to either receptor signaling or receptor endocytosis.

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