Department of Dermatology, University Medical Center Regensburg, 93053 Regensburg, Germany.
Institute of Pathology, University of Regensburg, 93053 Regensburg, Germany.
Int J Mol Sci. 2021 Jun 2;22(11):6024. doi: 10.3390/ijms22116024.
The acid-sensing ion channels ASIC1 and ASIC2, as well as the transient receptor potential vanilloid channels TRPV1 and TRPV4, are proton-gated cation channels that can be activated by low extracellular pH (pH), 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 ASIC1, ASIC2, TRPV1 and TRPV4 in malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and in nevus cell nevi (NCN). We conducted immunohistochemistry using paraffin-embedded tissue samples from patients and found that most skin tumors express ASIC1/2 and TRPV1/4. Striking results were that BCCs are often negative for ASIC2, while nearly all SCCs express this marker. Epidermal MM sometimes seem to lack ASIC1 in contrast to NCN. Dermal portions of MM show strong expression of TRPV1 more frequently than dermal NCN portions. Some NCN show a decreasing ASIC1/2 expression in deeper dermal tumor tissue, while MM seem to not lose ASIC1/2 in deeper dermal portions. ASIC1, ASIC2, TRPV1 and TRPV4 in skin tumors might be involved in tumor progression, thus being potential diagnostic and therapeutic targets.
酸感应离子通道 ASIC1 和 ASIC2 以及瞬时受体电位香草素通道 TRPV1 和 TRPV4 是质子门控阳离子通道，可被低细胞外 pH（pH）激活，这是实体瘤肿瘤微环境的标志。然而，这些通道在皮肤肿瘤发展中的作用尚不清楚。在这项研究中，我们研究了恶性黑色素瘤 (MM)、鳞状细胞癌 (SCC)、基底细胞癌 (BCC) 和痣细胞痣 (NCN) 中 ASIC1、ASIC2、TRPV1 和 TRPV4 的表达谱。我们使用来自患者的石蜡包埋组织样本进行免疫组织化学染色，发现大多数皮肤肿瘤表达 ASIC1/2 和 TRPV1/4。引人注目的结果是，BCC 通常为 ASIC2 阴性，而几乎所有 SCC 都表达该标志物。表皮 MM 与 NCN 相比，有时似乎缺乏 ASIC1。MM 的真皮部分比真皮 NCN 部分更频繁地表达强烈的 TRPV1。一些 NCN 在更深的真皮肿瘤组织中显示出 ASIC1/2 表达减少，而 MM 似乎在更深的真皮部分不丧失 ASIC1/2。皮肤肿瘤中的 ASIC1、ASIC2、TRPV1 和 TRPV4 可能参与肿瘤进展，因此是潜在的诊断和治疗靶点。
