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肝素结合表皮生长因子样生长因子在正常皮肤和皮肤癌中的免疫组织化学定位

Immunohistochemical localization of heparin-binding epidermal growth factor-like growth factor in normal skin and skin cancers.

作者信息

Downing M T, Brigstock D R, Luquette M H, Crissman-Combs M, Besner G E

机构信息

Department of Surgery, Ohio State University, Columbus 43205, USA.

出版信息

Histochem J. 1997 Oct;29(10):735-44. doi: 10.1023/a:1026417202351.

DOI:10.1023/a:1026417202351
PMID:9429077
Abstract

Heparin-binding epidermal growth factor (EGF)-like growth factor is a 22-kDa glycoprotein that was originally identified as a secreted product of cultured human macrophages. Although the growth factor mRNA has been identified in various cells and tissues, the tissue distribution of the protein itself has rarely been demonstrated. In this study, the EGF-like growth factor was detected immunohistochemically in a variety of human skin samples by indirect immunofluorescence using a polyclonal rabbit antiserum raised against residues 26-41 of mature heparin-binding EGF. The keratinocytes of a variety of epithelium-derived structures demonstrated reproducible, specific staining for the EGF. In normal tissues, this staining was prominent in the basal cells of the epidermis and in the epithelial cells lining epidermal appendages such as hair follicles, sebaceous sweat glands and eccrine sweat glands. In addition, specific staining was detected in skin cancers derived from the basal epithelial cell layer, including basal and squamous cell carcinomas of the skin, with no staining detected in melanoma specimens. Immunoreactive heparin-binding EGF was characteristically associated with the surface of cells. With minor exceptions, the immunoreactive sites are identical to the known EGF receptor distribution in the skin, and suggest that keratinocyte-derived heparin-binding EGF may act in concert with other EGF family members in processes such as skin morphogenesis and wound repair, as well as in the development of skin cancers.

摘要

肝素结合表皮生长因子(EGF)样生长因子是一种22 kDa的糖蛋白,最初被鉴定为培养的人巨噬细胞的分泌产物。尽管已在各种细胞和组织中鉴定出该生长因子的mRNA,但蛋白质本身的组织分布却鲜有报道。在本研究中,使用针对成熟肝素结合EGF的26 - 41位残基产生的兔多克隆抗血清,通过间接免疫荧光在多种人类皮肤样本中免疫组织化学检测到了EGF样生长因子。多种上皮来源结构的角质形成细胞对EGF呈现出可重复的特异性染色。在正常组织中,这种染色在表皮的基底细胞以及表皮附属器(如毛囊、皮脂腺和小汗腺)的上皮细胞中很明显。此外,在源自基底上皮细胞层的皮肤癌(包括皮肤基底细胞癌和鳞状细胞癌)中检测到特异性染色,而在黑色素瘤标本中未检测到染色。免疫反应性肝素结合EGF特征性地与细胞表面相关。除了少数例外,免疫反应位点与皮肤中已知的EGF受体分布相同,这表明角质形成细胞衍生的肝素结合EGF可能在皮肤形态发生、伤口修复以及皮肤癌的发生等过程中与其他EGF家族成员协同发挥作用。

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