Department of Dermatology, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
Center for Clinical Studies, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
Cells. 2021 Dec 23;11(1):27. doi: 10.3390/cells11010027.
TWIK-related acid-sensitive potassium channels TASK1 and TASK3, as well as the G-protein-coupled receptors GPR31 and GPR151, are proton-sensitive membrane proteins. They can be activated or inhibited by low extracellular pH (pHe), which is a hallmark of the tumor microenvironment in solid tumors. However, the role of these channels in the development of skin tumors is still unclear. In this study, we investigated the expression profiles of TASK1, TASK3, GPR31 and GPR151 in squamous cell carcinomas (SCCs), basal cell carcinomas (BCCs), nevus cell nevi (NCN), and malignant melanomas (MMs). We performed immunohistochemistry using paraffin-embedded tissue samples from patients and found that most skin tumors express TASK1/3 and GPR31/151. The results show that BCCs are often negative for GPR31/151 as well as for TASK1/3, while nearly all SCCs express these markers. MMs and NCN show similar expression patterns. However, some tumors show a decreasing TASK1/3 expression in deeper dermal tumor tissue, while GPCRs were expressed more evenly. The lower frequency of GPR31/151 and TSAK1/3 expression in BCCs when compared to SCCs is a novel histological feature distinguishing these two entities. Moreover, BCCs also show lower expression of GPR31/151 and TASK1/3 as compared to NCN and MMs.
TWIK 相关酸敏感钾通道 TASK1 和 TASK3 以及 G 蛋白偶联受体 GPR31 和 GPR151 是质子敏感的膜蛋白。它们可以被低细胞外 pH（pHe）激活或抑制，这是实体瘤肿瘤微环境的一个标志。然而，这些通道在皮肤肿瘤发展中的作用仍不清楚。在这项研究中，我们研究了 TASK1、TASK3、GPR31 和 GPR151 在鳞状细胞癌（SCCs）、基底细胞癌（BCCs）、痣细胞痣（NCN）和恶性黑色素瘤（MMs）中的表达谱。我们使用患者的石蜡包埋组织样本进行了免疫组织化学染色，发现大多数皮肤肿瘤表达 TASK1/3 和 GPR31/151。结果表明，BCC 通常对 GPR31/151 以及 TASK1/3 呈阴性，而几乎所有 SCC 均表达这些标志物。MMs 和 NCN 表现出相似的表达模式。然而，一些肿瘤在更深的真皮肿瘤组织中 TASK1/3 表达降低，而 GPCR 表达更为均匀。与 SCC 相比，BCC 中 GPR31/151 和 TSAK1/3 的表达频率较低是区分这两种实体的新组织学特征。此外，BCC 与 NCN 和 MMs 相比，GPR31/151 和 TASK1/3 的表达也较低。
