Inhibition of apoptosis in human tumour cells by the tumour-associated serpin, SCC antigen-1

• Published in: British journal of cancer Vol. 82; no. 4; pp. 981 - 989
• Main Authors: SUMINAMI, Y, NAGASHIMA, S, VUJANOVIC, N. L, HIRABAYASHI, K, KATO, H, WHITESIDE, T. L
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-02-2000
• Subjects: Antigens; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Antineoplastic agents; Apoptosis; Apoptosis - drug effects; Apoptosis - immunology; Base Sequence; Biological and medical sciences; Cancer; Carcinoma, Squamous Cell - immunology; Cells; Cervix; Cytokines; DNA Primers; General aspects; Head and Neck Neoplasms - immunology; Humans; Medical research; Medical sciences; Pharmacology. Drug treatments; Proteins; Regular; Serpins; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-TNF; United States > US; Pittsburgh Pennsylvania; Tumoral marker; Bronchopulmonary; Myeloproliferative syndrome; Alkaloid; Isomerases; Chronic myelocytic leukemia; Established cell line; Head and neck; Bronchus disease; ENT disease; Inhibition; Small cell carcinoma; Tumor necrosis factor α; Human; Lung disease; Squamous cell carcinoma; Tumor associated antigen; Serine endopeptidases; Respiratory disease; Enzyme; Cytokine; Rodentia; DNA topoisomerase; Enzyme inhibitor; Malignant hemopathy; Malignant tumor; Peptidases; Vertebrata; Chronic; Mammalia; Mouse; Cell death; Animal; LAK cell; Hydrolases; Apoptosis
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1054/bjoc.1999.1028

The squamous cell carcinoma antigen (SCC Ag) is a tumour-associated protein and a member of the serine protease inhibitor (serpin) family. The SCC Ag has been used as a serologic tumour marker for SCC progression, and its elevated serum levels are a risk factor for disease relapse. However, the biologic significance of this intracytoplasmic protein in cancer cells remains unknown. In this report, we demonstrated that apoptosis induced by 7-ethyl-10-hydroxycamptothecin, tumour necrosis factor-alpha (TNF-alpha) or interleukin (IL)-2-activated natural killer (NK) cells was significantly inhibited in tumour cells transduced with the SCC Ag-1 cDNA, as compared to control cells in vitro. Also, inhibition of the SCC Ag-1 expression in tumour cells by transfection of antisense SCC Ag-1 cDNA was accompanied by significantly increased sensitivity of these cells to apoptosis induced by etoposide or TNF-alpha. The mechanism of protection of tumour cells from apoptosis involved inhibition of caspase-3 activity and/or upstream proteases. In vivo, tumour cells overexpressing the SCC Ag-1 formed significantly larger tumours in nude mice than the SCC Ag-1-negative controls. Thus, overexpression of the SCC Ag-1, a member of the serpin family, in human cancer cells contributed to their survival by mediating protection from drug-, cytokine- or effector cell-induced apoptosis.