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Medical Molecular Morphology
Published in: Medical Molecular Morphology 4/2017

01-12-2017 | Review

Clinically relevant radioresistant cell line: a simple model to understand cancer radioresistance

Authors: Yoshikazu Kuwahara, Mehryar Habibi Roudkenar, Yusuke Urushihara, Yohei Saito, Kazuo Tomita, Amaneh Mohammadi Roushandeh, Tomoaki Sato, Akihiro Kurimasa, Manabu Fukumoto

Published in: Medical Molecular Morphology | Issue 4/2017

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Abstract

Radiotherapy (RT) is one of the major modalities for the treatment of human cancers and has been established as an excellent local treatment for malignant tumors. Conventional fractionated RT consists of 2-Gy X-rays, fractionated once a day, 5 days a week for 5–7 weeks in total 60 Gy. The efficacy of RT depends on the existence of radioresistant cells, which remains one of the most critical obstacles in RT and radio-chemotherapy. To improve the efficacy of RT, understanding the characteristics of radioresistant cells is one of the important subjects in radiation biology. Several studies have been reported to find out molecules implicated in radioresistance. However, it is noteworthy that cellular radioresistance has been mainly studied among cells with different genetic backgrounds and different origins. Therefore, making a system to compare between radioresistant and sensitive cells with the isogenic background is required. In this review, some aspects of cellular radioresistance mainly focusing on clinically relevant radioresistant (CRR) cell lines that can continue to proliferate even under exposure to 2-Gy X-rays, once a day, for more than 30 days, which is consistent with the conventional fractionated RT are discussed.
Literature
1.
2.
Andrä C, Rauch J, Li M, Ganswindt U, Belka C, Saleh-Ebrahimi L, Ballhausen H, Nachbichler SB, Roeder F (2015) Excellent local control and survival after postoperative or definitive radiation therapy for sarcomas of the head and neck. Radiat Oncol 10:140CrossRefPubMedPubMedCentral
3.
Gatcombe HG, Marcus RB Jr, Katzenstein HM, Tighiouart M, Esiashvili N (2009) Excellent local control from radiation therapy for high-risk neuroblastoma. Int J Radiat Oncol Biol Phys 74:1549–1554CrossRefPubMed
4.
Hara W, Loo BW Jr, Goffinet DR, Chang SD, Adler JR, Pinto HA, Fee WE, Kaplan MJ, Fischbein NJ, Le QT (2008) Excellent local control with stereotactic radiotherapy boost after external beam radiotherapy in patients with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 71:393–400CrossRefPubMed
5.
Glasser OWC (1995) Roentgen and the discovery of the Roentgen rays. AJR Am J Roentgenol 165:1033–1040CrossRefPubMed
6.
Bernier J, Hall EJ, Giaccia A (2004) Radiation oncology: a century of achievements. Nat Rev Cancer 4:737–747CrossRefPubMed
7.
8.
Azzam EI, Jay-Gerin JP, Pain D (2012) Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Lett 327:48–60CrossRefPubMed
9.
10.
Barcellos-Hoff MH, Park C, Wright EG (2005) Radiation and the microenvironment—tumorigenesis and therapy. Nat Rev Cancer 5:867–875CrossRefPubMed
11.
Peters LJ, Withers HR, Thames HD Jr, Fletcher GH (1982) Tumor radioresistance in clinical radiotherapy. Int J Radiat Oncol Biol Phys 8:101–108CrossRefPubMed
12.
Zhou S, Ye W, Shao Q, Zhang M, Liang J (2013) Nrf2 is a potential therapeutic target in radioresistance in human cancer. Crit Rev Oncol Hematol 88:706–715CrossRefPubMed
13.
Ogawa K, Murayama S, Mori M (2007) Predicting the tumor response to radiotherapy using microarray analysis. Oncol Rep 18:1243–1248PubMed
14.
Fang J, Zhou SH, Fan J, Yan SX (2015) Roles of glucose transporter-1 and the phosphatidylinositol 3kinase/protein kinase B pathway in cancer radioresistance. Mol Med Rep 11:1573–1581CrossRefPubMed
15.
Janikova M, Skarda J (2012) Differentiation pathways in carcinogenesis and in chemo- and radioresistance. Neoplasma 59:6–17CrossRefPubMed
16.
Hatanpaa KJ, Burma S, Zhao D, Habib AA (2010) Epidermal growth factor receptor in glioma: signal transduction, neuropathology, imaging, and radioresistance. Neoplasia 12:675–684CrossRefPubMedPubMedCentral
17.
Milas L, Raju U, Liao Z, Ajani J (2005) Targeting molecular determinants of tumor chemo-radioresistance. Semin Oncol 32:S78–S81CrossRefPubMed
18.
Jameel JK, Rao VS, Cawkwell L, Drew PJ (2004) Radioresistance in carcinoma of the breast. Breast 13:452–460CrossRefPubMed
19.
Shimura T, Ochiai Y, Noma N, Oikawa T, Sano Y, Fukumoto M (2013) Cyclin D1 overexpression perturbs DNA replication and induces replication-associated DNA double-strand breaks in acquired radioresistant cells. Cell Cycle 12:773–782CrossRefPubMedPubMedCentral
20.
Kuwahara Y, Li L, Baba T, Nakagawa H, Shimura T, Yamamoto Y, Ohkubo Y, Fukumoto M (2009) Clinically relevant radioresistant cells efficiently repair DNA double-strand breaks induced by X-rays. Cancer Sci 100:747–752CrossRefPubMed
21.
22.
Shimura T, Kakuda S, Ochiai Y, Nakagawa H, Kuwahara Y, Takai Y, Kobayashi J, Komatsu K, Fukumoto M (2010) Acquired radioresistance of human tumor cells by DNA-PK/AKT/GSK3beta-mediated cyclin D1 overexpression. Oncogene 29:4826–4837CrossRefPubMed
23.
Shimura T, Kakuda S, Ochiai Y, Kuwahara Y, Takai Y, Fukumoto M (2011) Targeting the AKT/GSK3beta/cyclin D1/Cdk4 survival signaling pathway for eradication of tumor radioresistance acquired by fractionated radiotherapy. Int J Radiat Oncol Biol Phys 80:540–548CrossRefPubMed
24.
Coco Martin JM, Balkenende A, Verschoor T, Lallemand F, Michalides R (1999) Cyclin D1 overexpression enhances radiation-induced apoptosis and radiosensitivity in a breast tumor cell line. Cancer Res 59:1134–1140PubMed
25.
McDermott N, Meunier A, Lynch TH, Hollywood D, Marignol L (2014) Isogenic radiation resistant cell lines: development and validation strategies. Int J Radiat Biol 90:115–126CrossRefPubMed
26.
de Llobet LI, Baro M, Figueras A, Modolell I, Da Silva MV, Muñoz P, Navarro A, Mesia R, Balart J (2013) Development and characterization of an isogenic cell line with a radioresistant phenotype. Clin Transl Oncol 15:189–197CrossRefPubMed
27.
28.
Puck TT, Morkovin D, Marcus PI, Cieciura SJ (1957) Action of X-rays on mammalian cells. II. Survival curves of cells from normal human tissues. J Exp Med 106:485–500CrossRefPubMedPubMedCentral
29.
Kuwahara Y, Mori M, Oikawa T, Shimura T, Ohtake Y, Mori S, Ohkubo Y, Fukumoto M (2010) The modified high-density survival assay is the useful tool to predict the effectiveness of fractionated radiation exposure. J Radiat Res 51:297–302CrossRefPubMed
30.
Xie L, Song X, Yu J, Wei L, Song B, Wang X, Lv L (2009) Fractionated irradiation induced radio-resistant esophageal cancer EC109 cells seem to be more sensitive to chemotherapeutic drugs. J Exp Clin Cancer Res 28:68CrossRefPubMedPubMedCentral
31.
Wei K, Kodym R, Jin C (1998) Radioresistant cell strain of human fibrosarcoma cells obtained after long-term exposure to X-rays. Radiat Environ Biophys 37:133–137CrossRefPubMed
32.
Qing Y, Yang XQ, Zhong ZY, Lei X, Xie JY, Li MX, Xiang DB, Li ZP, Yang ZZ, Wang G, Wang D (2010) Microarray analysis of DNA damage repair gene expression profiles in cervical cancer cells radioresistant to 252Cf neutron and X-rays. BMC Cancer 10:71CrossRefPubMedPubMedCentral
33.
Fukuda K, Sakakura C, Miyagawa K, Kuriu Y, Kin S, Nakase Y, Hagiwara A, Mitsufuji S, Okazaki Y, Hayashizaki Y, Yamagishi H (2004) Differential gene expression profiles of radioresistant oesophageal cancer cell lines established by continuous fractionated irradiation. Br J Cancer 91:1543–1550CrossRefPubMedPubMedCentral
34.
Masters JR (2002) HeLa cells 50 years on: the good, the bad and the ugly. Nat Rev Cancer 2:315–319CrossRefPubMed
35.
Pomp J, Wike JL, Ouwerkerk IJ, Hoogstraten C, Davelaar J, Schrier PI, Leer JW, Thames HD, Brock WA (1996) Cell density dependent plating efficiency affects outcome and interpretation of colony forming assays. Radiother Oncol 40:121–125CrossRefPubMed
36.
Born R, Kummermehr J, Griebel J, Trott KR (1995) The proliferative capacity of mouse fibrosarcoma cells that survived X-irradiation. Radiat Environ Biophys 34:233–237CrossRefPubMed
37.
Broerse JJ, MacVittie TJ (1984) Response of different species to total body irradiation. Springer, AmsterdamCrossRef
38.
39.
Dumont FJ, Bischoff P (2012) Disrupting the mTOR signaling network as a potential strategy for the enhancement of cancer radiotherapy. Curr Cancer Drug Targets 12:899–924CrossRefPubMed
40.
41.
Gewirtz DA, Hilliker ML, Wilson EN (2009) Promotion of autophagy as a mechanism for radiation sensitization of breast tumor cells. Radiother Oncol 92:323–328CrossRefPubMed
42.
Lefranc F, Facchini V, Kiss R (2007) Proautophagic drugs: a novel means to combat apoptosis-resistant cancers, with a special emphasis on glioblastomas. Oncologist 212:1395–1403CrossRef
43.
Nam HY, Han MW, Chang HW, Kim SY, Kim SW (2013) Prolonged autophagy by MTOR inhibitor leads radioresistant cancer cells into senescence. Autophagy 9:1631–1632CrossRefPubMed
44.
Kuwahara Y, Oikawa T, Ochiai Y, Roudkenar MH, Fukumoto M, Shimura T, Ohtake Y, Ohkubo Y, Mori S, Uchiyama Y, Fukumoto M (2011) Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy. Cell Death Dis 2:e177CrossRefPubMedPubMedCentral
45.
Kuwahara Y, Mori M, Kitahara S, Fukumoto M, Ezaki T, Mori S, Echigo S, Ohkubo Y, Fukumoto M (2014) Targeting of tumor endothelial cells combining 2 Gy/day of X-ray with Everolimus is the effective modality for overcoming clinically relevant radioresistant tumors. Cancer Med 3:310–321CrossRefPubMedPubMedCentral
46.
Vaupel P, Thews O, Hoeckel M (2001) Treatment resistance of solid tumors: role of hypoxia and anemia. Med Oncol 18:243–259CrossRefPubMed
47.
Bristow RG, Hill RP (2008) Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer 8:180–192CrossRefPubMed
48.
Dancey JE (2005) Inhibitors of the mammalian target of rapamycin. Expert Opin Investig Drugs 14:313–328CrossRefPubMed
49.
Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A, RECORD-1 Study Group (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456CrossRefPubMed
50.
Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, Witt O, Kohrman MH, Flamini JR, Wu JY, Curatolo P, de Vries PJ, Berkowitz N, Anak O, Niolat J, Jozwiak S (2014) Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med 363:1801–1811
51.
Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Öberg K, RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study Group (2011) Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364:514–523CrossRefPubMedPubMedCentral
52.
Banath JP, Macphail SH, Olive PL (2004) Radiation sensitivity, H2AX phosphorylation, and kinetics of repair of DNA strand breaks in irradiated cervical cancer cell lines. Cancer Res 64:7144–7149CrossRefPubMed
53.
Lynam-Lennon N, Reynolds JV, Pidgeon GP, Lysaght J, Marignol L, Maher SG (2010) Alterations in DNA repair efficiency are involved in the radioresistance of esophageal adenocarcinoma. Radiat Res 174:703–711CrossRefPubMed
54.
Schaue D, McBride WH (2005) Counteracting tumor radioresistance by targeting DNA repair. Mol Cancer Ther 4:1548–1550CrossRefPubMed
55.
Olive PL, Banath JP (2006) The comet assay: a method to measure DNA damage in individual cells. Nat Protoc 1:23–29CrossRefPubMed
56.
Wada S, Kurahayashi H, Kobayashi Y, Funayama T, Yamamoto K, Natsuhori M, Ito N (2003) The relationship between cellular radiosensitivity and radiation-induced DNA damage measured by the comet assay. J Vet Med Sci 65:471–477CrossRefPubMed
57.
Fukumoto M, Amanuma T, Kuwahara Y, Shimura T, Suzuki M, Mori S, Kumamoto H, Saito Y, Ohkubo Y, Duan Z, Sano K, Oguchi T, Kainuma K, Usami S, Kinoshita K, LeeI Fukumoto M (2014) Guanine nucleotide-binding protein 1 is one of the key molecules contributing to cancer cell radioresistance. Cancer Sci 105:1351–1359CrossRefPubMedPubMedCentral
58.
Kuwahara Y, Roudkenar MH, Suzuki M, Urushihara Y, Fukumoto M, Saito Y, Fukumoto M (2016) The involvement of mitochondrial membrane potential in cross-resistance between radiation and docetaxel. Int J Radiat Oncol Biol Phys 96:556–565CrossRefPubMed
59.
Takahashi A, Ma H, Nakagawa A, Yoshida Y, Kanai T, Ohno T, Kuwahara Y, Fukumoto M, Nakano T (2014) Carbon-ion beams efficiently induce cell killing in X-ray resistant human squamous tongue cancer cells. Int J Med Phys Clin Eng Radiat Oncol 3:133–142CrossRef
60.
Saito Y, Abiko R, Kishida A, Kuwahara Y, Yamamoto Y, Yamamoto F, Fukumoto M, Ohkubo Y (2015) Loss of EGF-dependent cell proliferation ability on radioresistant cell HepG2-8960-R. Cell Biochem Funct 33:73–79CrossRefPubMed
61.
Jing Z, Gong L, Xie CY, Zhang L, Su HF, Deng X, Wu SX (2009) Reverse resistance to radiation in KYSE-150R esophageal carcinoma cell after epidermal growth factor receptor signal pathway inhibition by cetuximab. Radiother Oncol 93:468–473CrossRefPubMed
62.
Bouras A, Kaluzova M, Hadjipanayis CG (2015) Radiosensitivity enhancement of radioresistant glioblastoma by epidermal growth factor receptor antibody-conjugated iron-oxide nanoparticles. J Neurooncol 124:13–22CrossRefPubMedPubMedCentral
63.
Diaz Miqueli A, Rolff J, Lemm M, Fichtner I, Perez R, Montero E (2009) Radiosensitisation of U87MG brain tumours by anti-epidermal growth factor receptor monoclonal antibodies. Br J Cancer 100:950–958CrossRefPubMedPubMedCentral
Metadata
Title
Clinically relevant radioresistant cell line: a simple model to understand cancer radioresistance
Authors
Yoshikazu Kuwahara
Mehryar Habibi Roudkenar
Yusuke Urushihara
Yohei Saito
Kazuo Tomita
Amaneh Mohammadi Roushandeh
Tomoaki Sato
Akihiro Kurimasa
Manabu Fukumoto
Publication date
01-12-2017
Publisher
Springer Japan
Published in
Medical Molecular Morphology / Issue 4/2017
Print ISSN: 1860-1480
Electronic ISSN: 1860-1499
DOI
https://doi.org/10.1007/s00795-017-0171-x

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