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gp130在皮肤肿瘤和炎症性疾病中的表达:其作为CD146(MUC18,Mel-CAM)身份的确切证据

Expression of gp130 in tumors and inflammatory disorders of the skin: formal proof of its identity as CD146 (MUC18, Mel-CAM).

作者信息

Schön Margarete, Kähne Thilo, Gollnick Harald, Schön Michael P

机构信息

Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine and Department of Dermatology, Julius Maximilians University, Würzburg, Germany.

出版信息

J Invest Dermatol. 2005 Aug;125(2):353-63. doi: 10.1111/j.0022-202X.2005.23808.x.

DOI:10.1111/j.0022-202X.2005.23808.x
PMID:16098047
Abstract

Two antibodies, BT14 and L101, detect a tumor-associated cell surface glycoprotein (gp130) whose properties in normal and diseased skin were assessed, and whose molecular identity was determined in this study. In normal skin, gp130 was constitutively expressed on dermal blood vessels and epidermal appendages, but not in interfollicular epidermis. Marked induction was detected within benign and malignant tumors of various origins including viral warts, basal cell carcinomas, squamous cell carcinomas, metastatic melanomas, and cutaneous T cell lymphomas. In vitro studies confirmed the general upregulation of gp130 expression in malignantly transformed cells. Surprisingly, gp130 was also induced in inflammatory skin diseases including psoriasis and allergic contact dermatitis. Halting proliferation of transformed keratinocytes through cytostatic drugs or increasing the Ca2+ concentration in the medium resulted in increased gp130 expression. In addition, overexpression of Bcl-2 led to upregulation of gp130. When the protein was purified and analyzed by peptide mass fingerprinting, we could demonstrate that it is MUC18 (Mel-CAM, CD146). Sequential immunoprecipitations and western blot analyses confirmed the identity of the antigen. Thus, both expression pattern and regulation characteristics of the now-known glycoprotein gp130 extended beyond previously published data regarding MUC18, thus shedding some new light on a supposedly well-known antigen.

摘要

两种抗体BT14和L101可检测到一种肿瘤相关细胞表面糖蛋白(gp130),本研究评估了其在正常皮肤和患病皮肤中的特性,并确定了其分子身份。在正常皮肤中,gp130在真皮血管和表皮附属器上组成性表达,但在毛囊间表皮中不表达。在包括病毒疣、基底细胞癌、鳞状细胞癌、转移性黑色素瘤和皮肤T细胞淋巴瘤在内的各种起源的良性和恶性肿瘤中均检测到明显诱导。体外研究证实了恶性转化细胞中gp130表达的普遍上调。令人惊讶的是,gp130在包括银屑病和过敏性接触性皮炎在内的炎症性皮肤病中也被诱导。通过细胞抑制药物阻止转化角质形成细胞的增殖或增加培养基中的Ca2+浓度会导致gp130表达增加。此外,Bcl-2的过表达导致gp130上调。当该蛋白被纯化并通过肽质量指纹图谱分析时,我们可以证明它是MUC18(Mel-CAM,CD146)。连续免疫沉淀和蛋白质印迹分析证实了抗原的身份。因此,现在已知的糖蛋白gp130的表达模式和调控特征超出了先前发表的关于MUC18的数据,从而为一种据称广为人知的抗原带来了一些新的启示。

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