Department of Health Sciences, Clinical Pharmacology and Oncology Unit, University of Florence, Florence, Italy.
Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
J Invest Dermatol. 2014 Sep;134(9):2408-2417. doi: 10.1038/jid.2014.145. Epub 2014 Mar 18.
A subgroup of the transient receptor potential (TRP) channels, including vanilloid 1 (TRPV1), TRPV2, TRPV3, TRPV4, and TRP ankyrin 1 (TRPA1), is expressed in cutaneous peptidergic somatosensory neurons, and has been found in skin non-neuronal cells, such as keratinocytes. Different cancer cells express TRPs, where they may exert either pro- or antitumorigenic roles. Expression and function of TRPs in skin cancers have been, however, poorly investigated. Here, we have studied the distribution and expression of TRPs by immunohistochemistry and messenger RNA (mRNA) in human healthy skin and human keratinocytic tumors, including intraepidermal proliferative disorders (solar keratosis (SK) and Bowen's disease), and non-melanoma skin cancer (NMSC; basal cell and squamous cell carcinomas). Similar TRPV1, TRPV2, and TRPV3 staining was found in keratinocytes from healthy and tumor tissues. TRPA1 staining was increased solely in SK samples. However, the marked TRPV4 staining and TRPV4 mRNA expression, observed in healthy or inflamed skin, was abrogated both in premalignant lesions and NMSC. In a human keratinocyte cell line (HaCaT), TRPV4 stimulation released IL-8, which in turn downregulated TRPV4 expression. Selective reduction in TRPV4 expression could represent an early biomarker of skin carcinogenesis. Whether the cytokine-dependent, autocrine pathway that results in TRPV4 downregulation contributes to NMSC mechanism remains to be determined.
瞬时受体电位 (TRP) 通道的亚组，包括香草素 1 (TRPV1)、TRPV2、TRPV3、TRPV4 和 TRP 锚蛋白 1 (TRPA1)，在皮肤肽能感觉神经元中表达，并在皮肤非神经元细胞中发现，如角质形成细胞。不同的癌细胞表达 TRP，它们可能发挥促癌或抑癌作用。然而，TRP 在皮肤癌中的表达和功能研究甚少。在这里，我们通过免疫组织化学和信使 RNA (mRNA) 研究了 TRP 在人正常皮肤和人角质形成细胞瘤中的分布和表达，包括表皮内增殖性疾病（太阳角化病 (SK) 和 Bowen 病）和非黑色素瘤皮肤癌（NMSC；基底细胞癌和鳞状细胞癌）。在来自健康和肿瘤组织的角质形成细胞中发现了相似的 TRPV1、TRPV2 和 TRPV3 染色。TRPA1 染色仅在 SK 样本中增加。然而，在健康或炎症皮肤中观察到的明显 TRPV4 染色和 TRPV4 mRNA 表达，在癌前病变和 NMSC 中均被消除。在人角质形成细胞系 (HaCaT) 中，TRPV4 刺激释放白细胞介素 8 (IL-8)，进而下调 TRPV4 表达。TRPV4 表达的选择性降低可能代表皮肤癌发生的早期生物标志物。导致 TRPV4 下调的细胞因子依赖性自分泌途径是否有助于 NMSC 机制仍有待确定。
