Biomaterial Database

Selective release of tumor necrosis factor binding protein II by malignant human epidermal cells reveals protection from tumor necrosis factor alpha-mediated cytotoxicity. 1994

P Neuner, and G Klosner, and M Pourmojib, and F Trautinger, and R Knobler

Department of Special and Environmental Dermatology, University of Vienna, Austria.

Most tumor cells produce both tumor necrosis factor (TNF) receptors, the M(r) 55,000 TNFRI and the M(r) 75,000 TNFRII, but they are mostly resistant to TNF-alpha-induced cytotoxicity. To gain further insight into the escape mechanisms of tumor cells from the harmful effect of TNF-alpha, we investigated the production of TNF-binding proteins (TNF-BPI, TNF-BPII, both M(r) 30,000) by malignant and normal epidermal cells and studied their functional role in TNF-alpha-induced cytotoxicity. Malignant human keratinocytes (A431, KB, HaCaT) and malignant human melanoma cells (KRFM) produced significant levels of both TNF-BPI and TNF-BPII on stimulation with phorbol myristate acetate. In contrast, normal human keratinocytes (HNK) and normal human melanocytes (HNM) released TNF-BPI but not TNF-BPII. The specific production of TNF-BPII in concert with TNF-BPI by the malignant cell lines revealed an inhibitory effect of supernatants on recombinant human TNF-alpha-mediated cytotoxicity of the TNF-dependent murine cell line L929, while supernatants of normal epidermal cells had no effect. Preincubation of supernatants with anti-TNF-BPI monoclonal antibody htr-9 or anti-TNF-BPII monoclonal antibody utr-1 reversed this inhibitory effect additively, indicating that the production of both TNF-BPs is necessary to protect cells from TNF-alpha-mediated cytotoxicity. A TNF-alpha scavanging effect of TNF-BPs resulting in subsequent inhibition of TNF-alpha binding to L929 cells could be demonstrated by ligand blotting and fluorescence-activated cell sorting analysis. Thus the production of TNF-BPII by epidermal tumor cells in concert with TNF-BPI appears to demonstrate a specific mechanism by which malignant epithelial cells escape from TNF-alpha-mediated cytotoxicity.

UI	MeSH Term	Description	Entries
D008544	Melanocytes	Mammalian pigment cells that produce MELANINS, pigments found mainly in the EPIDERMIS, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called MELANOSOMES. The large non-mammalian melanin-containing cells are called MELANOPHORES.	Melanocyte
D008545	Melanoma	A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)	Malignant Melanoma,Malignant Melanomas,Melanoma, Malignant,Melanomas,Melanomas, Malignant
D002352	Carrier Proteins	Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes.	Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000911	Antibodies, Monoclonal	Antibodies produced by a single clone of cells.	Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D012878	Skin Neoplasms	Tumors or cancer of the SKIN.	Cancer of Skin,Skin Cancer,Cancer of the Skin,Neoplasms, Skin,Cancer, Skin,Cancers, Skin,Neoplasm, Skin,Skin Cancers,Skin Neoplasm
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D014409	Tumor Necrosis Factor-alpha	Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.	Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D015603	Keratinocytes	Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.	Keratinocyte