This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Padovan, E. Articles by Heberer, M. Search for Related Content PubMed PubMed Citation Articles by Padovan, E. Articles by Heberer, M.

Interferon Stimulated Gene 15 Constitutively Produced by Melanoma Cells Induces E-Cadherin Expression on Human Dendritic Cells¹

Department of Surgical Research [E. P., A. R., M. B., G. C. S., M. H.] and Institute of Pathology [L. T.], University of Basel, 4031 Basel, Switzerland; Roche Genetics, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland [U. C.]; and The Cleveland Clinic Foundation, Cleveland, Ohio 44195 [B. J., E. C. B.]

The immunobiology of tumor-infiltrating dendritic cells (DCs) can be strongly influenced by the cytokine environment present in the malignant tissue. We have previously identified discrete melanoma lines, inducing E-cadherin expression on monocyte-derived DCs in vitro. We demonstrate here that this effect, independent of cell contact, is not inducible in the presence of tumor lysates and requires the constitutive expression of IFN stimulated gene 15 (ISG15) by malignant cells.

High-density oligonucleotide arrays were used to investigate the expression pattern of 7000 genes in RNA from two melanoma cell clones competent for E-cadherin induction and two clones devoid of DC-modulating capacity. A total of 13 genes encoding soluble proteins were expressed at higher magnitude in melanomas able to induce E-cadherin expression on DCs. Combining those data with quantitative protein assays, we could narrow our investigation down to three factors: the chemokine CCL5 and the cytokines ISG15 and type I IFNs. Strikingly, >7 ng/ml of ISG15 could be detected in the corresponding melanoma-conditioned medium and induction of E-cadherin on DCs failed in the presence of antibodies neutralizing ISG15 protein. Most importantly, strong cytoplasmic expression of ISG15 was detected by immunohistochemistry in the original tumor specimen from which the melanoma cell lines under investigation were derived.

These data describe a novel property of ISG15 targeting induction of E-cadherin on DCs and possibly influencing their migratory behavior.

This article has been cited by other articles:

				N. V. Giannakopoulos, E. Arutyunova, C. Lai, D. J. Lenschow, A. L. Haas, and H. W. Virgin ISG15 Arg151 and the ISG15-Conjugating Enzyme UbE1L Are Important for Innate Immune Control of Sindbis Virus J. Virol., February 15, 2009; 83(4): 1602 - 1610. [Abstract] [Full Text] [PDF]

				C. Lai, J. J. Struckhoff, J. Schneider, L. Martinez-Sobrido, T. Wolff, A. Garcia-Sastre, D.-E. Zhang, and D. J. Lenschow Mice Lacking the ISG15 E1 Enzyme UbE1L Demonstrate Increased Susceptibility to both Mouse-Adapted and Non-Mouse-Adapted Influenza B Virus Infection J. Virol., January 15, 2009; 83(2): 1147 - 1151. [Abstract] [Full Text] [PDF]

				S. D. Desai, L. M. Wood, Y.-C. Tsai, T.-S. Hsieh, J. R. Marks, G. L. Scott, B. C. Giovanella, and L. F. Liu ISG15 as a novel tumor biomarker for drug sensitivity Mol. Cancer Ther., June 1, 2008; 7(6): 1430 - 1439. [Abstract] [Full Text] [PDF]

				D. J. Lenschow, C. Lai, N. Frias-Staheli, N. V. Giannakopoulos, A. Lutz, T. Wolff, A. Osiak, B. Levine, R. E. Schmidt, A. Garcia-Sastre, et al. From the cover: IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis viruses PNAS, January 23, 2007; 104(4): 1371 - 1376. [Abstract] [Full Text] [PDF]

				D. J. Lenschow, N. V. Giannakopoulos, L. J. Gunn, C. Johnston, A. K. O'Guin, R. E. Schmidt, B. Levine, and H. W. Virgin IV Identification of Interferon-Stimulated Gene 15 as an Antiviral Molecule during Sindbis Virus Infection In Vivo J. Virol., November 15, 2005; 79(22): 13974 - 13983. [Abstract] [Full Text] [PDF]

				M. M. Joyce, F. J. White, R. C. Burghardt, J. J. Muniz, T. E. Spencer, F. W. Bazer, and G. A. Johnson Interferon Stimulated Gene 15 Conjugates to Endometrial Cytosolic Proteins and Is Expressed at the Uterine-Placental Interface throughout Pregnancy in Sheep Endocrinology, February 1, 2005; 146(2): 675 - 684. [Abstract] [Full Text] [PDF]

				K. Hoek, D. L. Rimm, K. R. Williams, H. Zhao, S. Ariyan, A. Lin, H. M. Kluger, A. J. Berger, E. Cheng, E. S. Trombetta, et al. Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas Cancer Res., August 1, 2004; 64(15): 5270 - 5282. [Abstract] [Full Text] [PDF]

				M. Gentile, L. Latonen, and M. Laiho Cell cycle arrest and apoptosis provoked by UV radiation-induced DNA damage are transcriptionally highly divergent responses Nucleic Acids Res., August 15, 2003; 31(16): 4779 - 4790. [Abstract] [Full Text] [PDF]