Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 4/2009

01-04-2009 | Original Article

Early developmental expression of a normally tumor-associated and drug-inhibited cell surface-located NADH oxidase (ENOX2) in non-cancer cells

Authors: NaMi Cho, D. James Morré

Published in: Cancer Immunology, Immunotherapy | Issue 4/2009

Login to get access

Abstract

Full length mRNA to a drug-inhibited cell surface NADH oxidase, tNOX or ENOX2, is present in both non-cancer and cancer cells but is translated only in cancer cells as alternatively spliced variants. ENOX2 is a growth-related protein of the external plasma membrane surface that is shed into the circulation and is inhibited by a series of quinone site inhibitors with anticancer activity. To test the possibility that ENOX2 expression might be important to early stages of non-cancer cell development, the expression of the protein was monitored in chicken embryos during their development. Polyclonal antisera to a 34 kDa human serum form of ENOX2 cross-immunoreactive with the drug-responsive NADH oxidase of chicken hepatoma cells was used. The protein was identified based on drug-responsive enzymatic activities and analyses by western blots. The drug-responsive activity was associated with plasma membranes and sera of early chicken embryos and with chicken hepatoma plasma membranes but was absent from plasma membranes prepared from livers or from sera of normal adult chickens and from late embryo stages. The findings suggest that ENOX2 may fulfill some functions essential to the growth of early embryos which are lost in late embryo stages and absent from normal adult cells but which then reappear in cancer.
Literature
1.
Morré DJ, Chueh P-J, Morré DM (1995) Capsaicin inhibits preferentially the NADH oxidase and growth of transformed cells in culture. Proc Natl Acad Sci USA 92:1831–1835PubMedCrossRef
2.
Morré DJ, Morré DM, Stevenson J, MacKellar WC, McClure D (1995) HeLa plasma membranes bind the antitumor sulfonylurea LY181984 with high affinity. Biochim Biophys Acta 1244:133–140PubMed
3.
Morré DJ, Kim C, Paulik M, Morré DM, Faulk WP (1997) Is the drug-responsive NADH oxidase of the cancer cell plasma membrane a molecular target for adriamycin? J Biomembr Bioenerg 29:269–280CrossRef
4.
Morré DJ (1998) NADH oxidase: a multifunctional ectoproteins of the eukaryotic cell surface. In: Asard H, Bérczi A, Caubergs R (eds) Plasma membrane redox systems and their role in biological stress and disease. Kluwer Academic Publishers, Dordrecht, The Netherlands, pp 121–156
5.
Morré DJ, Morré DM (2003) Cell surface NADH oxidases (ECTO-NOX proteins) with roles in cancer, cellular time-keeping, growth, aging and neurodegenerative disease. Free Radical Res 37:795–808CrossRef
6.
Morré DJ, Merriman R, Tanzer LR, Wu L-Y, Morré DM, MacKellar WC (1995) Inhibition of the NADH oxidase activity of plasma membranes isolated from xenografts and cell lines by the antitumor sulfonylurea, N-(4-methlyphenylsulfonyl)-N′-(4-chlorophenyl)urea (LY181984) correlates with drug susceptibility of growth. Protoplasma 184:203–208CrossRef
7.
Morré DJ, Sun E, Geilen C, Wu L-Y, de Cabo R, Krasagakis K, Orfanos CE, Morré DM (1996) Capsaicin inhibits plasma membrane NADH oxidase and growth of human and mouse melanoma lines. Eur J Cancer 32:1995–2003CrossRef
8.
Chueh P-J, Kim C, Cho N, Morré DM, Morré DJ (2002) Molecular cloning and characterization of a tumor-associated, growth-related and time-keeping hydroquinone (NADH) oxidase (NOX) of the HeLa cell surface. Biochemistry 41:3732–3741PubMedCrossRef
9.
Morré DJ, Caldwell S, Mayorga A, Wu L-Y, Morré DM (1997) NADH oxidase activity from sera altered by capsaicin is widely distributed among cancer patients. Arch Biochem Biophys 342:224–230PubMedCrossRef
10.
Morré DJ, Reust T (1997) A circulating form of NADH oxidase activity responsive to the antitumor sulfonylurea N-(4-methlyphenylsulfonyl)-N′-(4-chlorophenyl)urea (LY181984) specific to sera from cancer patients. J Bioenerg Biomemb 29:281–289CrossRef
11.
Kishi T, Morré DM, Morré DJ (1999) The plasma membrane NADH oxidase of HeLa cells has hydroquinone oxidase activity. Biochim Biophys Acta 1412:66–77PubMedCrossRef
12.
Morré DJ, Pogue R, Morré DM (1999) A multi-functional ubiquinol oxidase of the external cell surface and sera. BioFactors 9:179–187PubMedCrossRef
13.
Herst PM, Berridge MV (2006) Plasma membrane electron transport: a new target for cancer drug development. Curr Mol Med 6:895–904PubMedCrossRef
14.
Tang X, Tian Z, Chueh P-J, Chen S, Morré DM, Morré DJ (2007) Alternative splicing as the basis for specific localization of tNOX, a unique hydroquinone (NADH) oxidase, to the cancer cell surface. Biochemistry 46:12,337–12346
15.
Hamburger V, Hamilton HL (1951) A series of normal stages in the development of the chick embryo. J Morphol 88:49–92CrossRef
16.
Scholz E, Welniak E, Nyholm T, Guo P (1993) An avian hepatoma cell line for the cultivation of infectious laryngotracheitis virus and for the expression of foreign genes with a mammalian promoter. J Virol Methods 43(3):273–286PubMedCrossRef
17.
Morre DJ, Morre DM (1989) Preparation of mammalian plasma membranes by aqueous two-phase partition. BioTechniques 7(9):946–958PubMed
18.
Wilkinson FE, Kim C, Cho N, Chueh P-J, Leslie S, Moya-Camarena S, Wu L-Y, Morré DM, Morré DJ (1996) Isolation and identification of a protein with capsaicin-inhibited NADH oxidase activity from culture media conditioned by growth of HeLa cells. Arch Biochem Biophys 336:275–282PubMedCrossRef
19.
Chueh P-J, Morré DJ, Wilkinson FE, Gibson J, Morré DM (1997) A 33.5 kDa heat- and protease-resistant NADH oxidase inhibited by capsaicin from sera of cancer patients. Arch Biochem Biophys 342:38–47PubMedCrossRef
20.
Schreiber H, Ward PL, Rowley DA, Stauss HJ (1988) Unique tumor-specific antigens. Annu Rev Immunol 6:465–482PubMedCrossRef
21.
Mizejewski GJ (2001) Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants. Exp Biol Med 226:377–408
22.
Lucha PA Jr, Rosen L, Olenwine JA, Reed JF 3rd, Riether RD, Stasik JJ Jr, Khubchandani IT (1997) Value of carcinoembryonic antigen monitoring in curative surgery for recurrent colorectal carcinoma. Dis Colon Rectum 40:145–149PubMedCrossRef
23.
Huang JQ, Turbide C, Daniels E, Jothy S, Beauchemin N (1990) Spatiotemporal expression of murine carcinoembryonic antigen (CEA) gene family members during mouse embryogenesis. Development 110:573–588PubMed
24.
Gitlin D, Perricelli A, Gitlin GM (1972) Synthesis of α-fetoprotein by liver, yolk sac, and gastrointestinal tract of the human conceptus. Cancer Res 32(5):979–982PubMed
25.
Yagiz K, Morré DJ, Morré DM (2006) Transgenic mouse line overexpressing the cancer-specific tNOX protein has an enhanced growth and acquired drug-response phenotype. J Nutr Biochem 17:750–759PubMedCrossRef
26.
Bearz A, Talamini R, Vaccher E, Spina M, Simonelli C, Steffan A, Berretta M, Chimienti E, Tirelli U (2007) MUC-1 (CA 15–3 antigen) as a highly reliable predictor of response to EGFR inhibitors in patients with bronchioloalveolar carcinoma: an experience on 26 patients. Int J Biol Markers 22:307–311PubMed
27.
Braga VM, Gendler SJ (1993) Modulation of Muc-1 mucin expression in the mouse uterus during the estrus cycle, early pregnancy and placentation. J Cell Sci 105(Pt 2):397–405PubMed
28.
Brown JP, Woodbury RG, Hart CE, Hellström I, Hellström KE (1981) Quantitative analysis of melanoma-associated antigen p97 in normal and neoplastic tissues. Proc Natl Acad Sci USA 78(1):539–543PubMedCrossRef
29.
Disis M, Pupa SM, Gralow JR, Dittadi R, Menard S, Cheever MA (1997) High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer. J Clin Oncol 15:3363–3367PubMed
30.
Morré DJ, Wilkinson FE, Kim C, Cho N, Lawrence J, Morré DM (1996) Antitumor sulfonylurea-inhibited NADH oxidase of cultured HeLa cells shed into media. Biochim Biophys Acta 1280:197–206PubMedCrossRef
Metadata
Title
Early developmental expression of a normally tumor-associated and drug-inhibited cell surface-located NADH oxidase (ENOX2) in non-cancer cells
Authors
NaMi Cho
D. James Morré
Publication date
01-04-2009
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 4/2009
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-008-0577-3

Other articles of this Issue 4/2009

Cancer Immunology, Immunotherapy 4/2009 Go to the issue

Original Article

Interferon regulatory factor 8 mediates tumor-induced inhibition of antigen processing and presentation by dendritic cells

Original Article

In vivo anti-melanoma efficacy of allo-restricted CTLs specific for melanoma expanded by artificial antigen-presenting cells

Original Article

Conversion of murine antibodies to human antibodies and their optimization for ovarian cancer therapy targeted to the folate receptor

Erratum

In vivo anti-melanoma efficacy of allo-restricted CTLs specific for melanoma expanded by artificial antigen-presenting cells

Original Article

High expression of PGE2 enzymatic pathways in cervical (pre)neoplastic lesions and functional consequences for antigen-presenting cells

Original Article

Antigen-presenting cells containing multiple costimulatory molecules promote activation and expansion of human antigen-specific memory CD8+ T cells
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits