Skip to main content
Erschienen in: Clinical Oral Investigations 3/2018

15.10.2017 | Original Article

MAGE-A11 expression contributes to cisplatin resistance in head and neck cancer

verfasst von: Stefan Hartmann, Leonie Zwick, Mario J. J. Scheurer, Andreas R. Fuchs, Roman C. Brands, Axel Seher, Hartmut Böhm, Alexander C. Kübler, Urs D. A. Müller-Richter

Erschienen in: Clinical Oral Investigations | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

Objective

The objective of this study is to investigate the roles of melanoma-associated antigens (MAGEs) in the cisplatin treatment of head and neck cancer.

Materials and methods

We assessed the efficacy of cisplatin in a set of four head and neck cancer cell lines using a crystal violet assay. The MAGE-A expression in all cell lines was measured with RT-qPCR. The correlation between MAGE-A expression and cisplatin efficacy was investigated using Spearman’s correlation analysis. Furthermore, we established a cell line with stable overexpression of MAGE-A11 and determined influence on proliferation, cisplatin efficacy and cell apoptosis. In this cell line, the effects of cisplatin were assessed using either crystal violet assays or flow cytometry (Annexin V).

Results

For MAGE-A11, we observed the highest correlation (r = 1.000, p = 0.0417) with low cisplatin efficacy. Stable overexpression of MAGE-A11 resulted in no changes in proliferation, but in lower cisplatin cytotoxicity and lower rates of apoptosis. Also, mouse double minute 2 homolog (MDM2) expression was induced by MAGE-A11 overexpression.

Conclusion

We provide evidence that MAGE-A11 expression contributes to cisplatin resistance in head and neck cancer.

Clinical relevance

Our study underscores the negative predictive role of MAGE-A11 expression in head and neck cancer.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde BJ, Knuth A, Boon T (2007) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. J Immunol 178(5):2617–2621PubMed van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde BJ, Knuth A, Boon T (2007) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. J Immunol 178(5):2617–2621PubMed
5.
Zurück zum Zitat Scanlan MJ, Simpson AJ, Old LJ (2004) The cancer/testis genes: review, standardization, and commentary. Cancer Immun 4:1PubMed Scanlan MJ, Simpson AJ, Old LJ (2004) The cancer/testis genes: review, standardization, and commentary. Cancer Immun 4:1PubMed
9.
Zurück zum Zitat Chen X, Wang L, Yue D, Liu J, Huang L, Yang L, Cao L, Qin G, Li A, Wang D, Wang M, Qi Y, Zhang B, van der Bruggen P, Zhang Y (2016) Correlation between the high expression levels of cancer-germline genes with clinical characteristics in esophageal squamous cell carcinoma. Histol Histopathol 32(8):793–803. doi:10.14670/HH-11-847 Chen X, Wang L, Yue D, Liu J, Huang L, Yang L, Cao L, Qin G, Li A, Wang D, Wang M, Qi Y, Zhang B, van der Bruggen P, Zhang Y (2016) Correlation between the high expression levels of cancer-germline genes with clinical characteristics in esophageal squamous cell carcinoma. Histol Histopathol 32(8):793–803. doi:10.​14670/​HH-11-847
10.
Zurück zum Zitat Hashimoto R, Kanda M, Takami H, Shimizu D, Oya H, Hibino S, Okamura Y, Yamada S, Fujii T, Nakayama G, Sugimoto H, Koike M, Nomoto S, Fujiwara M, Kodera Y (2015) Aberrant expression of melanoma-associated antigen-D2 serves as a prognostic indicator of hepatocellular carcinoma outcome following curative hepatectomy. Oncol Lett 9(3):1201–1206. https://doi.org/10.3892/ol.2014.2823 CrossRefPubMed Hashimoto R, Kanda M, Takami H, Shimizu D, Oya H, Hibino S, Okamura Y, Yamada S, Fujii T, Nakayama G, Sugimoto H, Koike M, Nomoto S, Fujiwara M, Kodera Y (2015) Aberrant expression of melanoma-associated antigen-D2 serves as a prognostic indicator of hepatocellular carcinoma outcome following curative hepatectomy. Oncol Lett 9(3):1201–1206. https://​doi.​org/​10.​3892/​ol.​2014.​2823 CrossRefPubMed
12.
Zurück zum Zitat Laban S, Giebel G, Klumper N, Schrock A, Doescher J, Spagnoli G, Thierauf J, Theodoraki MN, Remark R, Gnjatic S, Krupar R, Sikora AG, Litjens G, Grabe N, Kristiansen G, Bootz F, Schuler PJ, Brunner C, Bragelmann J, Hoffmann TK, Perner S (2017) MAGE expression in head and neck squamous cell carcinoma primary tumors, lymph node metastases and respective recurrences-implications for immunotherapy. Oncotarget 8(9):14719–14735. 10.18632/oncotarget.14830 CrossRefPubMedPubMedCentral Laban S, Giebel G, Klumper N, Schrock A, Doescher J, Spagnoli G, Thierauf J, Theodoraki MN, Remark R, Gnjatic S, Krupar R, Sikora AG, Litjens G, Grabe N, Kristiansen G, Bootz F, Schuler PJ, Brunner C, Bragelmann J, Hoffmann TK, Perner S (2017) MAGE expression in head and neck squamous cell carcinoma primary tumors, lymph node metastases and respective recurrences-implications for immunotherapy. Oncotarget 8(9):14719–14735. 10.​18632/​oncotarget.​14830 CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Yang B, O'Herrin SM, Wu J, Reagan-Shaw S, Ma Y, Bhat KM, Gravekamp C, Setaluri V, Peters N, Hoffmann FM, Peng H, Ivanov AV, Simpson AJ, Longley BJ (2007) MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines. Cancer Res 67(20):9954–9962. https://doi.org/10.1158/0008-5472.CAN-07-1478 CrossRefPubMed Yang B, O'Herrin SM, Wu J, Reagan-Shaw S, Ma Y, Bhat KM, Gravekamp C, Setaluri V, Peters N, Hoffmann FM, Peng H, Ivanov AV, Simpson AJ, Longley BJ (2007) MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines. Cancer Res 67(20):9954–9962. https://​doi.​org/​10.​1158/​0008-5472.​CAN-07-1478 CrossRefPubMed
22.
Zurück zum Zitat Ang KK, Chen A, Curran WJ Jr, Garden AS, Harari PM, Murphy BA, Wong SJ, Bellm LA, Schwartz M, Newman J, Adkins D, Hayes DN, Parvathaneni U, Brachman D, Ghabach B, Schneider CJ, Greenberg M, Anne PR (2012) Head and neck carcinoma in the United States: first comprehensive report of the longitudinal oncology registry of head and neck carcinoma (LORHAN). Cancer 118(23):5783–5792. https://doi.org/10.1002/cncr.27609 CrossRefPubMed Ang KK, Chen A, Curran WJ Jr, Garden AS, Harari PM, Murphy BA, Wong SJ, Bellm LA, Schwartz M, Newman J, Adkins D, Hayes DN, Parvathaneni U, Brachman D, Ghabach B, Schneider CJ, Greenberg M, Anne PR (2012) Head and neck carcinoma in the United States: first comprehensive report of the longitudinal oncology registry of head and neck carcinoma (LORHAN). Cancer 118(23):5783–5792. https://​doi.​org/​10.​1002/​cncr.​27609 CrossRefPubMed
23.
24.
Zurück zum Zitat Ries J, Schultze-Mosgau S, Neukam F, Diebel E, Wiltfang J (2005) Investigation of the expression of melanoma antigen-encoding genes (MAGE-A1 to -A6) in oral squamous cell carcinomas to determine potential targets for gene-based cancer immunotherapy. Int J Oncol 26(3):817–824PubMed Ries J, Schultze-Mosgau S, Neukam F, Diebel E, Wiltfang J (2005) Investigation of the expression of melanoma antigen-encoding genes (MAGE-A1 to -A6) in oral squamous cell carcinomas to determine potential targets for gene-based cancer immunotherapy. Int J Oncol 26(3):817–824PubMed
27.
Zurück zum Zitat Cuffel C, Rivals JP, Zaugg Y, Salvi S, Seelentag W, Speiser DE, Lienard D, Monnier P, Romero P, Bron L, Rimoldi D (2011) Pattern and clinical significance of cancer-testis gene expression in head and neck squamous cell carcinoma. Int J Cancer 128(11):2625–2634. https://doi.org/10.1002/ijc.25607 CrossRefPubMed Cuffel C, Rivals JP, Zaugg Y, Salvi S, Seelentag W, Speiser DE, Lienard D, Monnier P, Romero P, Bron L, Rimoldi D (2011) Pattern and clinical significance of cancer-testis gene expression in head and neck squamous cell carcinoma. Int J Cancer 128(11):2625–2634. https://​doi.​org/​10.​1002/​ijc.​25607 CrossRefPubMed
32.
Zurück zum Zitat Momand J, Zambetti GP, Olson DC, George D, Levine AJ (1992) The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69(7):1237–1245CrossRefPubMed Momand J, Zambetti GP, Olson DC, George D, Levine AJ (1992) The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69(7):1237–1245CrossRefPubMed
35.
Zurück zum Zitat Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375(19):1856–1867. https://doi.org/10.1056/NEJMoa1602252 CrossRefPubMedPubMedCentral Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375(19):1856–1867. https://​doi.​org/​10.​1056/​NEJMoa1602252 CrossRefPubMedPubMedCentral
36.
Metadaten
Titel
MAGE-A11 expression contributes to cisplatin resistance in head and neck cancer
verfasst von
Stefan Hartmann
Leonie Zwick
Mario J. J. Scheurer
Andreas R. Fuchs
Roman C. Brands
Axel Seher
Hartmut Böhm
Alexander C. Kübler
Urs D. A. Müller-Richter
Publikationsdatum
15.10.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Oral Investigations / Ausgabe 3/2018
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-017-2242-8

Weitere Artikel der Ausgabe 3/2018

Clinical Oral Investigations 3/2018 Zur Ausgabe

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

07.05.2024 Klinik aktuell Nachrichten

Extreme Arbeitsverdichtung und kaum Supervision: Dr. Andrea Martini, Sprecherin des Bündnisses Junge Ärztinnen und Ärzte (BJÄ) über den Frust des ärztlichen Nachwuchses und die Vorteile des Rucksack-Modells.

Endlich: Zi zeigt, mit welchen PVS Praxen zufrieden sind

IT für Ärzte Nachrichten

Darauf haben viele Praxen gewartet: Das Zi hat eine Liste von Praxisverwaltungssystemen veröffentlicht, die von Nutzern positiv bewertet werden. Eine gute Grundlage für wechselwillige Ärztinnen und Psychotherapeuten.

Parodontalbehandlung verbessert Prognose bei Katheterablation

19.04.2024 Vorhofflimmern Nachrichten

Werden Personen mit Vorhofflimmern in der Blanking-Periode nach einer Katheterablation gegen eine bestehende Parodontitis behandelt, verbessert dies die Erfolgsaussichten. Dafür sprechen die Resultate einer prospektiven Untersuchung.

Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Zahnmedizin und bleiben Sie gut informiert – ganz bequem per eMail.