An Xiangjie, Xu Guangfen, Yang Liu, Wang Yuejue, Li Yan, McHepange Uwesu O, Shen Guanxin, Tu Yating, Tao Juan
Department of Dermatology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Dermatol. 2014 Jan;41(1):76-83. doi: 10.1111/1346-8138.12314. Epub 2013 Dec 20.
The hypoxia-inducible factor-1 (HIF-1α) pathway is associated with tumor growth, angiogenesis and metastasis in various carcinomas. Little is known regarding the role of the HIF-1α signaling pathway in cutaneous squamous cell carcinoma (SCC). We investigated the expression of HIF-1α, vascular endothelial growth factor (VEGF) and the HIF negative regulator, prolyl hydroxylase domain protein 2 (PHD2), in cutaneous SCC, Bowen's disease, seborrheic keratosis (SK) and normal skin by immunohistochemistry and in situ hybridization. Additionally, we explored the relationships between these factors and the clinical and histological characteristics of each disease. Our study indicated that the expression of HIF-1α and VEGF was significantly higher (P < 0.05) in cutaneous SCC than in Bowen's disease, SK or normal skin. In contrast, PHD2 showed significantly higher expression in normal skin compared with SK, Bowen's disease and cutaneous SCC (P < 0.05). Grade II-IV cutaneous SCC had higher expression levels of nuclear HIF-1α and cytoplasm VEGF protein but less nuclear PHD2 protein than grade Ι cutaneous SCC (P < 0.05). Overexpression of HIF-1α and VEGF, as well as the decreased expression of PHD2, may play important roles in the development of cutaneous SCC.
缺氧诱导因子-1（HIF-1α）通路与多种癌症的肿瘤生长、血管生成和转移相关。关于HIF-1α信号通路在皮肤鳞状细胞癌（SCC）中的作用，目前所知甚少。我们通过免疫组织化学和原位杂交技术，研究了HIF-1α、血管内皮生长因子（VEGF）以及HIF负调节因子脯氨酰羟化酶结构域蛋白2（PHD2）在皮肤SCC、鲍恩病、脂溢性角化病（SK）和正常皮肤中的表达情况。此外，我们还探讨了这些因子与每种疾病的临床和组织学特征之间的关系。我们的研究表明，皮肤SCC中HIF-1α和VEGF的表达明显高于鲍恩病、SK或正常皮肤（P < 0.05）。相反，与SK、鲍恩病和皮肤SCC相比，PHD2在正常皮肤中的表达明显更高（P < 0.05）。与Ⅰ级皮肤SCC相比，Ⅱ - Ⅳ级皮肤SCC的核HIF-1α和细胞质VEGF蛋白表达水平更高，但核PHD2蛋白表达更少（P < 0.05）。HIF-1α和VEGF的过表达以及PHD2表达的降低可能在皮肤SCC的发生发展中起重要作用。
