Werner Christoph, Dirsch Olaf, Dahmen Uta, Grimm Marc-Oliver, Schulz Stefan, Lupp Amelie
Department of Internal Medicine III, Jena University Hospital, Jena, Germany; Institute of Pharmacology and Toxicology, Jena University Hospital, Jena, Germany.
Institute of Pathology, Jena University Hospital, Jena, Germany; Institute of Pathology, Klinikum Chemnitz, Chemnitz, Germany.
Transl Oncol. 2020 Sep;13(9):100801. doi: 10.1016/j.tranon.2020.100801. Epub 2020 May 24.
Prostate cancer (PCa) is the most common type of cancer among men in Western countries. Despite numerous therapeutic options, few treatments are available for patients with end-stage disease. In the present study, different somatostatin receptors (SSTs) and the chemokine receptor CXCR4 were evaluated for their suitability as novel therapeutic targets in PCa.
The expression of SST subtypes 1, 2A, 3, and 5 and of CXCR4 was evaluated in 276 PCa tumor samples on a tissue microarray (TMA) in 23 whole-block tumor samples and in 3 PCa cell lines by immunohistochemistry using well-characterized monoclonal antibodies.
Overall, the frequency and intensity of expression of SSTs and CXCR4 were very low among the PCa samples investigated. Specifically, SST5, SST2A, and SST3 were expressed, albeit at low intensity, in 10.5%, 9.1%, and 0.7% of the TMA samples, respectively. None of the TMA samples showed SST1 or CXCR4 expression. Only a single small-cell-type neuroendocrine carcinoma that was coincidentally included among the whole-block samples exhibited strong SST2A, SST5, and CXCR4 and moderate SST3 expression. Independent of the tumor cells, the tumor capillaries in many of the PCa samples were strongly positive for SST2A, SST3, SST5, or CXCR4 expression. SST expression in the tumor cells was associated with advanced tumor grade and stage.
Overall, SST and CXCR4 expression levels are clearly of no therapeutic relevance in PCa. SST- or CXCR4-based therapy might be feasible, however, in rare cases of small-cell-type neuroendocrine carcinoma of the prostate.
前列腺癌（PCa）是西方国家男性中最常见的癌症类型。尽管有众多治疗选择，但针对晚期疾病患者的治疗方法却很少。在本研究中，评估了不同的生长抑素受体（SSTs）和趋化因子受体CXCR4作为PCa新型治疗靶点的适用性。
使用特征明确的单克隆抗体，通过免疫组织化学在276个PCa肿瘤样本的组织微阵列（TMA）、23个整块肿瘤样本以及3个PCa细胞系中评估SST亚型1、2A、3和5以及CXCR4的表达。
总体而言，在所研究的PCa样本中，SSTs和CXCR4的表达频率和强度非常低。具体而言，SST5、SST2A和SST3在TMA样本中的表达率分别为10.5%、9.1%和0.7%，尽管强度较低。没有TMA样本显示SST1或CXCR4表达。仅在整块样本中偶然包含的一个小细胞型神经内分泌癌显示出强烈的SST2A、SST5和CXCR4表达以及中等强度的SST3表达。与肿瘤细胞无关，许多PCa样本中的肿瘤毛细血管SST2A、SST3、SST5或CXCR4表达呈强阳性。肿瘤细胞中的SST表达与肿瘤的高级别和晚期相关。
总体而言，SST和CXCR4表达水平在PCa中显然没有治疗相关性。然而，基于SST或CXCR4的治疗在罕见的前列腺小细胞型神经内分泌癌病例中可能是可行的。
