Expression of gp130 in tumors and inflammatory disorders of the skin: formal proof of its identity as CD146 (MUC18, Mel-CAM).
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.
Schön
Margarete
M
Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine and Department of Dermatology, Julius Maximilians University, Würzburg, Germany.
Kähne
Thilo
T
Gollnick
Harald
H
Schön
Michael P
MP
D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D015153:Blotting, Western; D051929:CD146 Antigen; D002280:Basal Cell Carcinoma / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000378:metabolism; D020405:Dermis / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D047468:Immunoprecipitation; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000032:analysis / Q000378:metabolism*; D010449:Peptide Mapping; D011565:Psoriasis / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism*
D015703:Antigens, CD; D051929:CD146 Antigen; C497902:MCAM protein, human; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D019158:N-Acetylneuraminic Acid