Institute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Str. 1, 07747, Jena, Germany.
Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany.
J Cancer Res Clin Oncol. 2018 Jul;144(7):1227-1237. doi: 10.1007/s00432-018-2645-1. Epub 2018 Apr 25.
Glioblastomas represent the most common primary malignant tumor of the nervous system and the most frequent type of astrocytic tumors. Despite improved therapeutic options, prognosis has remained exceptionally poor over the last two decades. Therefore, new treatment approaches are urgently needed. An overexpression of somatostatin (SST) as well as chemokine CXCR4 and endothelin A (ETA) receptors has been shown for many types of cancer. Respective expression data for astrocytic brain tumors, however, are scarce and contradictory.
SST subtype, CXCR4 and ETA expression was comparatively evaluated in a total of 57 grade I-IV astrocytic tumor samples by immunohistochemistry using well-characterized monoclonal antibodies.
Overall, receptor expression on the tumor cells was only very low. SST5 was the most prominently expressed receptor, followed by SST3, ETA, SST2 and CXCR4. In contrast, tumor capillaries displayed strong SST2, SST3, SST5, CXCR4 and ETA expression. Presence of SST5, CXCR4 and ETA on tumor cells and of SST3, CXCR4 and ETA on microvessels gradually increased from grade II to grade IV tumors. Ki-67 values correlated significantly with CXCR4 expression on tumor cells and with vascular SST3, CXCR4 or ETA positivity. SST5 or CXCR4 positivity of tumor cells and vascular SST3 or CXCR4 expression negatively correlated with patient outcome.
Though having some prognostic value, SST, CXCR4 or ETA expression on astrocytic tumor cells is clearly of no therapeutic relevance. Indirect targeting of these highly vascularized tumors via SST3, SST5, CXCR4 or ETA on the microvessels, in contrast, may represent a promising additional therapeutic strategy.
胶质母细胞瘤是最常见的原发性神经恶性肿瘤，也是最常见的星形细胞瘤类型。尽管治疗选择有所改善，但在过去的二十年中，预后仍然非常差。因此，迫切需要新的治疗方法。许多类型的癌症都表现出生长抑素（SST）以及趋化因子 CXCR4 和内皮素 A（ETA）受体的过度表达。然而，星形细胞瘤的相应表达数据却很少且相互矛盾。
通过免疫组织化学方法，使用经过充分验证的单克隆抗体，比较性地评估了总共 57 例 I-IV 级星形细胞瘤样本中的 SST 亚型、CXCR4 和 ETA 表达。
总体而言，肿瘤细胞上的受体表达水平非常低。SST5 是表达最明显的受体，其次是 SST3、ETA、SST2 和 CXCR4。相比之下，肿瘤毛细血管显示出强烈的 SST2、SST3、SST5、CXCR4 和 ETA 表达。SST5、CXCR4 和 ETA 存在于肿瘤细胞上，SST3、CXCR4 和 ETA 存在于微血管上，从 II 级肿瘤逐渐增加到 IV 级肿瘤。Ki-67 值与肿瘤细胞上的 CXCR4 表达以及血管 SST3、CXCR4 或 ETA 阳性呈显著相关。肿瘤细胞上的 SST5 或 CXCR4 阳性和血管 SST3 或 CXCR4 表达与患者预后呈负相关。
尽管具有一定的预后价值，但星形细胞瘤细胞上的 SST、CXCR4 或 ETA 表达显然与治疗无关。相反，通过微血管上的 SST3、SST5、CXCR4 或 ETA 对这些高度血管化的肿瘤进行间接靶向治疗，可能是一种有前途的附加治疗策略。
