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01-05-2020 | NSCLC | Original Article

Evaluating the immunoproteasome as a potential therapeutic target in cisplatin-resistant small cell and non-small cell lung cancer

Authors: Tetsuaki Shoji, Eiki Kikuchi, Junko Kikuchi, Yuta Takashima, Megumi Furuta, Hirofumi Takahashi, Kosuke Tsuji, Makie Maeda, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Jun Sakakibara-Konishi, Satoshi Konno

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2020

Abstract

Purpose

We evaluated the expression of proteasome subunits to assess whether the proteasome could be a therapeutic target in cisplatin-resistant lung cancer cells.

Methods

Cisplatin-resistant (CR) variants were established from three non-small cell lung cancer (NSCLC) cell lines (A549, H1299, and H1975) and two small cell lung cancer (SCLC) cell lines (SBC3 and SBC5). The expression of proteasome subunits, the sensitivity to immunoproteasome inhibitors, and 20S proteasomal proteolytic activity were examined in the CR variants of the lung cancer cell lines.

Results

All five CR cell lines highly expressed one or both of the immunoproteasome subunit genes, PSMB8 and PSMB9, while no clear trend was observed in the expression of constitutive proteasome subunits. The CR cells expressed significantly higher levels of PSMB8 and PSMB9 proteins, as well. The CR variants of the H1299 and SBC3 cell lines were more sensitive to immunoproteasome inhibitors, and had significantly more proteasomal proteolytic activity than their parental counterparts.

Conclusions

The immunoproteasome may be an effective therapeutic target in a subset of CR lung cancers. Proteasomal proteolytic activity may be a predictive marker for the efficacy of immunoproteasome inhibitors in cisplatin-resistant SCLC and NSCLC.

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Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108. https://doi.org/10.3322/caac.21262 CrossRefPubMed

Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69(1):7–34. https://doi.org/10.3322/caac.21551 CrossRefPubMed

Herbst RS, Heymach JV, Lippman SM (2008) Lung cancer. N Engl J Med 359(13):1367–1380. https://doi.org/10.1056/NEJMra0802714 CrossRefPubMed

Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ, Wu Y-L, Paz-Ares L (2017) Lung cancer: current therapies and new targeted treatments. Lancet 389(10066):299–311. https://doi.org/10.1016/s0140-6736(16)30958-8 CrossRefPubMed

Tay RY, Heigener D, Reck M, Califano R (2019) Immune checkpoint blockade in small cell lung cancer. Lung Cancer 137:31–37. https://doi.org/10.1016/j.lungcan.2019.08.024 CrossRefPubMed

Amable L (2016) Cisplatin resistance and opportunities for precision medicine. Pharmacol Res 106:27–36. https://doi.org/10.1016/j.phrs.2016.01.001 CrossRefPubMed

Basu A, Krishnamurthy S (2010) Cellular responses to cisplatin-induced DNA damage. J Nucleic Acids. https://doi.org/10.4061/2010/201367 CrossRefPubMedPubMedCentral

Brozovic A, Ambriović-Ristov A, Osmak M (2010) The relationship between cisplatin-induced reactive oxygen species, glutathione, and BCL-2 and resistance to cisplatin. Crit Rev Toxicol 40(4):347–359. https://doi.org/10.3109/10408441003601836 CrossRefPubMed

Mandic A, Hansson J, Linder S, Shoshan MC (2003) Cisplatin induces endoplasmic reticulum stress and nucleus-independent apoptotic signaling. J Biol Chem 278(11):9100–9106. https://doi.org/10.1074/jbc.M210284200 CrossRefPubMed

10.

Cocetta V, Ragazzi E, Montopoli M (2019) Mitochondrial involvement in cisplatin resistance. Int J Mol Sci. https://doi.org/10.3390/ijms20143384 CrossRefPubMedPubMedCentral

11.

Wangpaichitr M, Sullivan EJ, Theodoropoulos G, Wu C, You M, Feun LG, Lampidis TJ, Kuo MT, Savaraj N (2012) The relationship of thioredoxin-1 and cisplatin resistance: its impact on ROS and oxidative metabolism in lung cancer cells. Mol Cancer Ther 11(3):604–615. https://doi.org/10.1158/1535-7163.MCT-11-0599 CrossRefPubMedPubMedCentral

12.

Xu Y, Yu H, Qin H, Kang J, Yu C, Zhong J, Su J, Li H, Sun L (2012) Inhibition of autophagy enhances cisplatin cytotoxicity through endoplasmic reticulum stress in human cervical cancer cells. Cancer Lett 314(2):232–243. https://doi.org/10.1016/j.canlet.2011.09.034 CrossRefPubMed

13.

Martins I, Kepp O, Schlemmer F, Adjemian S, Tailler M, Shen S, Michaud M, Menger L, Gdoura A, Tajeddine N, Tesniere A, Zitvogel L, Kroemer G (2011) Restoration of the immunogenicity of cisplatin-induced cancer cell death by endoplasmic reticulum stress. Oncogene 30(10):1147–1158. https://doi.org/10.1038/onc.2010.500 CrossRefPubMed

14.

Xu Y, Wang C, Li Z (2014) A new strategy of promoting cisplatin chemotherapeutic efficiency by targeting endoplasmic reticulum stress. Mol Clin Oncol 2(1):3–7. https://doi.org/10.3892/mco.2013.202 CrossRefPubMed

15.

Murata S, Takahama Y, Kasahara M, Tanaka K (2018) The immunoproteasome and thymoproteasome: functions, evolution and human disease. Nat Immunol 19(9):923–931. https://doi.org/10.1038/s41590-018-0186-z CrossRefPubMed

16.

Nikesitch N, Lee JM, Ling S, Roberts TL (2018) Endoplasmic reticulum stress in the development of multiple myeloma and drug resistance. Clin Transl Immunol 7(1):e1007. https://doi.org/10.1002/cti2.1007 CrossRef

17.

Aki M, Shimbara N, Takashina M, Akiyama K, Kagawa S, Tamura T, Tanahashi N, Yoshimura T, Tanaka K, Ichihara A (1994) Interferon-gamma induces different subunit organizations and functional diversity of proteasomes. J Biochem 115(2):257–269. https://doi.org/10.1093/oxfordjournals.jbchem.a124327 CrossRefPubMed

18.

Hallermalm K, Seki K, Wei C, Castelli C, Rivoltini L, Kiessling R, Levitskaya J (2001) Tumor necrosis factor-alpha induces coordinated changes in major histocompatibility class I presentation pathway, resulting in increased stability of class I complexes at the cell surface. Blood 98(4):1108–1115CrossRefPubMed

19.

Thomas S, Kotamraju S, Zielonka J, Harder DR, Kalyanaraman B (2007) Hydrogen peroxide induces nitric oxide and proteosome activity in endothelial cells: a bell-shaped signaling response. Free Radic Biol Med 42(7):1049–1061. https://doi.org/10.1016/j.freeradbiomed.2007.01.005 CrossRefPubMedPubMedCentral

20.

Pickering AM, Koop AL, Teoh CY, Ermak G, Grune T, Davies KJ (2010) The immunoproteasome, the 20S proteasome and the PA28alphabeta proteasome regulator are oxidative-stress-adaptive proteolytic complexes. Biochem J 432(3):585–594. https://doi.org/10.1042/BJ20100878 CrossRefPubMed

21.

Groettrup M, Kirk CJ, Basler M (2010) Proteasomes in immune cells: more than peptide producers? Nat Rev Immunol 10(1):73–78. https://doi.org/10.1038/nri2687 CrossRefPubMed

22.

Nathan JA, Spinnenhirn V, Schmidtke G, Basler M, Groettrup M, Goldberg AL (2013) Immuno- and constitutive proteasomes do not differ in their abilities to degrade ubiquitinated proteins. Cell 152(5):1184–1194. https://doi.org/10.1016/j.cell.2013.01.037 CrossRefPubMedPubMedCentral

23.

Gandolfi S, Laubach JP, Hideshima T, Chauhan D, Anderson KC, Richardson PG (2017) The proteasome and proteasome inhibitors in multiple myeloma. Cancer Metastasis Rev 36(4):561–584. https://doi.org/10.1007/s10555-017-9707-8 CrossRefPubMed

24.

Roeten MSF, Cloos J, Jansen G (2018) Positioning of proteasome inhibitors in therapy of solid malignancies. Cancer Chemother Pharmacol 81(2):227–243. https://doi.org/10.1007/s00280-017-3489-0 CrossRefPubMed

25.

Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San-Miguel JF, Bladé J, Boccadoro M, Cavenagh J, Dalton WS, Boral AL, Esseltine DL, Porter JB, Schenkein D, Anderson KC, Assessment of Proteasome Inhibition for Extending Remission (APEX) Investigators (2005) Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352(24):2487–2498. https://doi.org/10.1056/NEJMoa043445 CrossRefPubMed

26.

Dimopoulos MA, Goldschmidt H, Niesvizky R, Joshua D, Chng W-J, Oriol A, Orlowski RZ, Ludwig H, Facon T, Hajek R, Weisel K, Hungria V, Minuk L, Feng S, Zahlten-Kumeli A, Kimball AS, Moreau P (2017) Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol 18(10):1327–1337. https://doi.org/10.1016/s1470-2045(17)30578-8 CrossRefPubMed

27.

Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, Sandhu I, Ganly P, Baker BW, Jackson SR, Stoppa AM, Simpson DR, Gimsing P, Palumbo A, Garderet L, Cavo M, Kumar S, Touzeau C, Buadi FK, Laubach JP, Berg DT, Lin J, Di Bacco A, Hui AM, van de Velde H, Richardson PG, Group T-MS (2016) Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 374(17):1621–1634. https://doi.org/10.1056/NEJMoa1516282 CrossRefPubMed

28.

Drilon A, Schoenfeld AJ, Arbour KC, Litvak A, Ni A, Montecalvo J, Yu HA, Panora E, Ahn L, Kennedy M, Haughney-Siller A, Miller V, Ginsberg M, Ladanyi M, Arcila M, Rekhtman N, Kris MG, Riely GJ (2019) Exceptional responders with invasive mucinous adenocarcinomas: a phase 2 trial of bortezomib in patients with KRAS G12D-mutant lung cancers. Cold Spring Harb Mol Case Stud. https://doi.org/10.1101/mcs.a003665 CrossRefPubMedPubMedCentral

29.

Papadopoulos KP, Burris HA III, Gordon M, Lee P, Sausville EA, Rosen PJ, Patnaik A, Cutler RE Jr, Wang Z, Lee S, Jones SF, Infante JR (2013) A phase I/II study of carfilzomib 2–10-min infusion in patients with advanced solid tumors. Cancer Chemother Pharmacol 72(4):861–868. https://doi.org/10.1007/s00280-013-2267-x CrossRefPubMedPubMedCentral

30.

Lara PN Jr, Chansky K, Davies AM, Franklin WA, Gumerlock PH, Gualianone PP, Atkins JN, Farneth N, Mack PC, Crowley JJ, Gandara DR (2006) Bortezomib (PS-341) in relapsed or refractory extensive stage small cell lung cancer: a Southwest Oncology Group phase II trial (S0327). J Thorac Oncol 1(9):996–1001CrossRefPubMed

31.

Arnold SM, Chansky K, Leggas M, Thompson MA, Villano JL, Hamm J, Sanborn RE, Weiss GJ, Chatta G, Baggstrom MQ (2017) Phase 1b trial of proteasome inhibitor carfilzomib with irinotecan in lung cancer and other irinotecan-sensitive malignancies that have progressed on prior therapy (Onyx IST reference number: CAR-IST-553). Investig New Drugs 35(5):608–615. https://doi.org/10.1007/s10637-017-0441-4 CrossRef

32.

Vermes I, Haanen C, Reutelingsperger C (2000) Flow cytometry of apoptotic cell death. J Immunol Methods 243(1–2):167–190. https://doi.org/10.1016/s0022-1759(00)00233-7 CrossRefPubMed

33.

Suzuki M, Yamamori T, Yasui H, Inanami O (2016) Effect of MPS1 inhibition on genotoxic stress responses in murine tumour cells. Anticancer Res 36(6):2783–2792PubMed

34.

Suzuki M, Yamamori T, Bo T, Sakai Y, Inanami O (2017) MK-8776, a novel Chk1 inhibitor, exhibits an improved radiosensitizing effect compared to UCN-01 by exacerbating radiation-induced aberrant mitosis. Transl Oncol 10(4):491–500. https://doi.org/10.1016/j.tranon.2017.04.002 CrossRefPubMedPubMedCentral

35.

Takashima Y, Kikuchi E, Kikuchi J, Suzuki M, Kikuchi H, Maeda M, Shoji T, Furuta M, Kinoshita I, Dosaka-Akita H, Sakakibara-Konishi J, Konno S (2019) Bromodomain and extraterminal domain inhibition synergizes with WEE1-inhibitor AZD1775 effect by impairing nonhomologous end joining and enhancing DNA damage in nonsmall cell lung cancer. Int J Cancer. https://doi.org/10.1002/ijc.32515 CrossRefPubMed

36.

Rouette A, Trofimov A, Haberl D, Boucher G, Lavallee VP, D'Angelo G, Hebert J, Sauvageau G, Lemieux S, Perreault C (2016) Expression of immunoproteasome genes is regulated by cell-intrinsic and -extrinsic factors in human cancers. Sci Rep 6:34019. https://doi.org/10.1038/srep34019 CrossRefPubMedPubMedCentral

37.

Niewerth D, Franke NE, Jansen G, Assaraf YG, van Meerloo J, Kirk CJ, Degenhardt J, Anderl J, Schimmer AD, Zweegman S, de Haas V, Horton TM, Kaspers GJ, Cloos J (2013) Higher ratio immune versus constitutive proteasome level as novel indicator of sensitivity of pediatric acute leukemia cells to proteasome inhibitors. Haematologica 98(12):1896–1904. https://doi.org/10.3324/haematol.2013.092411 CrossRefPubMedPubMedCentral

38.

Niewerth D, Kaspers GJ, Jansen G, van Meerloo J, Zweegman S, Jenkins G, Whitlock JA, Hunger SP, Lu X, Alonzo TA, van de Ven PM, Horton TM, Cloos J (2016) Proteasome subunit expression analysis and chemosensitivity in relapsed paediatric acute leukaemia patients receiving bortezomib-containing chemotherapy. J Hematol Oncol 9(1):82. https://doi.org/10.1186/s13045-016-0312-z CrossRefPubMedPubMedCentral

39.

Niewerth D, Kaspers GJ, Jansen G, van Meerloo J, Zweegman S, Jenkins G, Whitlock JA, Hunger SP, Lu X, Alonzo TA, van de Ven PM, Horton TM, Cloos J (2014) Interferon-γ-induced upregulation of immunoproteasome subunit assembly overcomes bortezomib resistance in human hematological cell lines. J Hematol Oncol. https://doi.org/10.1186/1756-8722-7-7 CrossRefPubMedPubMedCentral

40.

Busse A, Kraus M, Na IK, Rietz A, Scheibenbogen C, Driessen C, Blau IW, Thiel E, Keilholz U (2008) Sensitivity of tumor cells to proteasome inhibitors is associated with expression levels and composition of proteasome subunits. Cancer 112(3):659–670. https://doi.org/10.1002/cncr.23224 CrossRefPubMed

41.

Ji CH, Kwon YT (2017) Crosstalk and interplay between the ubiquitin-proteasome system and autophagy. Mol Cells 40(7):441–449. https://doi.org/10.14348/molcells.2017.0115 CrossRefPubMedPubMedCentral

42.

Zaffagnini G, Martens S (2016) Mechanisms of selective autophagy. J Mol Biol 428(9):1714–1724. https://doi.org/10.1016/j.jmb.2016.02.004 CrossRefPubMedPubMedCentral

43.

Ling YH, Liebes L, Jiang JD, Holland JF, Elliott PJ, Adams J, Muggia FM, Perez-Soler R (2003) Mechanisms of proteasome inhibitor PS-341-induced G(2)-M-phase arrest and apoptosis in human non-small cell lung cancer cell lines. Clin Cancer Res 9(3):1145–1154PubMed

44.

Zang L, Boufraqech M, Lake R, Kebebew E (2016) Carfilzomib potentiates CUDC-101-induced apoptosis in anaplastic thyroid cancer. Oncotarget 7(13):16517–16528. https://doi.org/10.18632/oncotarget.7760 CrossRef

45.

Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13(12):1501–1512. https://doi.org/10.1101/gad.13.12.1501 CrossRefPubMed

Title: Evaluating the immunoproteasome as a potential therapeutic target in cisplatin-resistant small cell and non-small cell lung cancer
Authors: Tetsuaki Shoji
Eiki Kikuchi
Junko Kikuchi
Yuta Takashima
Megumi Furuta
Hirofumi Takahashi
Kosuke Tsuji
Makie Maeda
Ichiro Kinoshita
Hirotoshi Dosaka-Akita
Jun Sakakibara-Konishi
Satoshi Konno
Publication date: 01-05-2020
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
Lung Cancer
Lung Cancer
NSCLC
SCLC
Lung Cancer
SCLC
Published in: Cancer Chemotherapy and Pharmacology / Issue 5/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04061-9

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