The proton-sensing GPCRs (pH-GPCRs) GPR4 (GPR19), TDAG8 (GPR65, T-cell death associated gene 8), OGR1 (GPR68, ovarian cancer GPCR1), and G2A (GPR132, G2 accumulation protein) are involved in sensing and transducing changes in extracellular pH (pH_e). Extracellular acidification is a central hallmark of solid cancer. pH-GPCR function has been associated with cancer cell proliferation, adhesion, migration and metastasis, as well as with modulation of the immune system. Little is known about the expression levels and role of pH-GPCRs in skin cancer. To better understand the functions of pH-GPCRs in skin cancer in vivo, we examined the expression-profiles of GPR4, TDAG8, OGR1 and G2A in four common skin tumors, i.e. squamous cell carcinoma (SCC), malignant melanoma (MM), compound nevus cell nevi (NCN), basal cell carcinoma (BCC). We performed immunohistochemistry and immunofluorescence staining on paraffin-embedded tissue samples acquired from patients suffering from SCC, MM, NCN or BCC. We show the expression of pH-GPCRs in four common skin cancers. Different expression patterns in the investigated skin cancer types indicate that the different pH-GPCRs may have distinct functions in tumor progression and serve as novel therapeutic targets.

质子感应 GPCR (pH-GPCR) GPR4 (GPR19)、TDAG8（GPR65，T 细胞死亡相关基因 8）、OGR1（GPR68，卵巢癌 GPCR1）和 G2A（GPR132，G2 积累蛋白）参与传感并转导细胞外 pH 值 (pH _e ) 的变化。细胞外酸化是实体癌的核心标志。 pH-GPCR 功能与癌细胞增殖、粘附、迁移和转移以及免疫系统的调节有关。关于 pH-GPCR 在皮肤癌中的表达水平和作用知之甚少。为了更好地了解pH-GPCR在体内皮肤癌中的功能，我们检测了四种常见皮肤肿瘤中GPR4、TDAG8、OGR1和G2A的表达谱，即鳞状细胞癌（SCC）、恶性黑色素瘤（MM）、化合物痣细胞痣（NCN）、基底细胞癌（BCC）。我们对取自 SCC、MM、NCN 或 BCC 患者的石蜡包埋组织样本进行了免疫组织化学和免疫荧光染色。我们展示了四种常见皮肤癌中 pH-GPCR 的表达。所研究的皮肤癌类型中的不同表达模式表明，不同的 pH-GPCR 在肿瘤进展中可能具有不同的功能，并可作为新的治疗靶点。