Mizutani Yoko, Iwamoto Ikuko, Kanoh Hiroyuki, Seishima Mariko, Nagata Koh-ichi
Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan.
Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Japan.
Histol Histopathol. 2014 Jun;29(6):757-66. doi: 10.14670/HH-29.757. Epub 2013 Dec 18.
Drebrin, an F-actin binding protein, is known to play important roles in cell migration, synaptogenesis and neural plasticity. Although drebrin was long thought to be specific for neuronal cells, its expression has recently been reported in non-neuronal cells. As for skin-derived cells, drebrin was shown to be enriched at adhering junctions (AJs) in cultured primary keratinocytes and also be highly expressed in basal cell carcinoma (BCC) cells. Since BCC and two types of benign neoplasm, trichoblastoma and trichoepithelioma, are considered to derive from the same origin, follicular germinative cells, it is sometimes difficult to morphologically distinguish BCC from trichoblastoma and trichoepithelioma. In this study, we performed immunohistochemical staining of drebrin in BCC, trichoblastoma and trichoepithelioma, to examine whether drebrin could serve as a biomarker for BCC diagnosis. In western blotting, drebrin was detected highly and moderately in the lysates from a squamous cell carcinoma cell line, DJM-1, and normal human epidermis, respectively. In immunofluorescence analyses, drebrin was colocalized with markers of AJs and tight junctions in DJM-1 cells and detected at cell-cell junction areas of human normal epidermis tissue. We then examined the distribution patterns of drebrin in BCC, trichoblastoma and trichoepithelioma. In BCC tissues, intense and homogeneous drebrin expression was observed mainly at tumor cell-cell boundaries. In contrast, drebrin was stained only weakly and non-homogeneously in trichoblastoma and trichoepthelioma tissue samples. For differential diagnosis of BCC, drebrin may be a novel and useful marker.
肌动蛋白结合蛋白drebrin在细胞迁移、突触形成和神经可塑性中发挥着重要作用。尽管长期以来人们一直认为drebrin是神经元细胞所特有的,但最近有报道称其在非神经元细胞中也有表达。至于皮肤来源的细胞,drebrin在培养的原代角质形成细胞的黏附连接(AJs)处富集,并且在基底细胞癌(BCC)细胞中也高度表达。由于BCC与两种良性肿瘤毛母细胞瘤和毛发上皮瘤被认为起源相同,均来自毛囊生发细胞,因此有时在形态学上难以将BCC与毛母细胞瘤和毛发上皮瘤区分开来。在本研究中,我们对BCC、毛母细胞瘤和毛发上皮瘤进行了drebrin免疫组织化学染色,以检查drebrin是否可作为BCC诊断的生物标志物。在蛋白质印迹法中,在鳞状细胞癌细胞系DJM-1和正常人表皮的裂解物中分别高度和中度检测到drebrin。在免疫荧光分析中,drebrin在DJM-1细胞中与AJs和紧密连接的标志物共定位,并在人正常表皮组织的细胞间连接区域检测到。然后我们检查了drebrin在BCC、毛母细胞瘤和毛发上皮瘤中的分布模式。在BCC组织中,主要在肿瘤细胞间边界观察到强烈且均匀的drebrin表达。相比之下,在毛母细胞瘤和毛发上皮瘤组织样本中,drebrin染色仅微弱且不均匀。对于BCC的鉴别诊断,drebrin可能是一种新颖且有用的标志物。