Quantitative proteomic analysis of single or fractionated radiation-induced proteins in human breast cancer MDA-MB-231 cells

Cell & Bioscience

Jie-Young Song¹  Dae-Seog Lim⁴  Seon Young Nam³  Sungkwan An²  Hee-Jong Woo⁵  Sang-Gu Hwang¹  Jiyeon Ahn¹  Seung-Youn Jung¹  Mi-Hyoung Kim⁵ 

[1] Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul 139-706, Korea;Department of Microbiological Engineering, Kon-Kuk University, Seoul, Korea;Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd, Seoul, Korea;Department of Applied Bioscience, CHA University, Gyeonggi-do, Korea;Laboratory of Immunology, College of Veterinary Medicine, Seoul National University, Seoul, Korea

关键词: SILAC;    Radiation therapy;    Proteomics;    Breast cancer;   

Others  :  1149209
DOI  :  10.1186/2045-3701-5-2

 received in 2014-08-25, accepted in 2014-12-02,  发布年份 2015

【 摘 要 】

Background

Radiotherapy is widely used to treat cancer alone or in combination with surgery, chemotherapy, and immunotherapy. However, damage to normal tissues and radioresistance of tumor cells are major obstacles to successful radiotherapy. Furthermore, the immune network around tumors appears to be connected to tumor progression and recurrence.

Methods

We investigated the cytosolic proteins produced by irradiated tumor cells by using a quantitative proteomic approach based on stable isotope labeling by amino acids in cell culture. MDA-MB-231 breast cancer cells were treated with a single or fractionated 10 Gray dose of ¹³⁷Cs γ-radiation, which was selected based on cell viability.

Results

Radiation-induced proteins were differentially expressed based on the fractionated times of radiation and were involved in multiple biological functions, including energy metabolism and cytoskeleton organization. We identified 46 proteins increased by at least 1.3-fold, and high ranks were determined for cathepsin D, gelsolin, arginino-succinate synthase 1, peroxiredoxin 5, and C-type mannose receptor 2.

Conclusion

These results suggest that a number of tumor-derived factors upregulated by γ-radiation are promising targets for modulation of the immune response during radiation treatment.

【 授权许可】

   
2015 Kim et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]Ahmad SS, Duke S, Jena R, Williams MV, Burnet NG: Advances in radiotherapy. BMJ 2012, 345:e7765.
• [2]Begg AC, Stewart FA, Vens C: Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer 2011, 11:239-253.
• [3]Delaney G, Jacob S, Featherstone C, Barton M: The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer 2005, 104:1129-1137.
• [4]Baskar R, Lee KA, Yeo R, Yeoh K-W: Cancer and radiation therapy: current advances and future directions. Int J Med Sci 2012, 9:193-199.
• [5]Berrington De Gonzalez A, Gilbert E, Curtis R, Inskip P, Kleinerman R, Morton L, Rajaraman P, Little MP: Second solid cancers after radiation therapy: a systematic review of the epidemiologic studies of the radiation dose-response relationship. Int J Radiat Oncol Biol Phys 2013, 86:224-233.
• [6]Jereczek-Fossa BA, Marsiglia HR, Orecchia R: Radiotherapy-related fatigue. Crit Rev Oncol Hematol 2002, 41:317-325.
• [7]Vacchelli E, Vitale I, Tartour E, Eggermont A, Sautès-Fridman C, Galon J, Zitvogel L, Kroemer G, Galluzzi L: Trial watch: anticancer radioimmunotherapy. Oncoimmunol 2013, 2:e25595.
• [8]Ogawa K, Yoshioka Y, Isohashi F, Seo Y, Yoshida K, Yamazaki H: Radiotherapy targeting cancer stem cells: current views and future perspectives. Anticancer Res 2013, 33:747-754.
• [9]Levy A, Chargari C, Cheminant M, Simon N, Bourgier C, Deutsch E: Radiation therapy and immunotherapy: implications for a combined cancer treatment. Crit Rev Oncol Hematol 2013, 85:278-287.
• [10]Holland R, Veling SH, Mravunac M, Hendriks JH: Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast-conserving surgery. Cancer 1985, 56:979-990.
• [11]Mann M: Functional and quantitative proteomics using SILAC. Nat Rev Mol Cell Biol 2006, 7:952-958.
• [12]Stenberg J, Rüetschi U, Skiöldebrand E, Kärrholm J, Lindahl A: Quantitative proteomics reveals regulatory differences in the chondrocyte secretome from human medial and lateral femoral condyles in osteoarthritic patients. Proteome Sci 2013, 11:43. BioMed Central Full Text
• [13]Zeng X, Yang P, Chen B, Jin X, Liu Y, Zhao X, Liang S: Quantitative secretome analysis reveals the interactions between epithelia and tumor cells by in vitro modulating colon cancer microenvironment. J Proteomics 2013, 89:51-70.
• [14]Keller A, Nesvizhskii AI, Kolker E, Aebersold R: Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal Chem 2002, 74:5383-5392.
• [15]Nesvizhskii AI, Keller A, Kolker E, Aebersold R: A statistical model for identifying proteins by tandem mass spectrometry. Anal Chem 2003, 75:4646-4658.
• [16]Basu S, Binder RJ, Suto R, Anderson KM, Srivastava PK: Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int Immunol 2000, 12:1539-1546.
• [17]Verbakel WFAR, van den Berg J, Slotman BJ, Sminia P: Comparable cell survival between high dose rate flattening filter free and conventional dose rate irradiation. Acta Oncol Stockh Swed 2013, 52:652-657.
• [18]John-Aryankalayil M, Palayoor ST, Cerna D, Simone CB, Falduto MT, Magnuson SR, Coleman CN: Fractionated radiation therapy can induce a molecular profile for therapeutic targeting. Radiat Res 2010, 174:446-458.
• [19]John-Aryankalayil M, Palayoor ST, Makinde AY, Cerna D, Simone CB, Falduto MT, Magnuson SR, Coleman CN: Fractionated radiation alters oncomir and tumor suppressor miRNAs in human prostate cancer cells. Radiat Res 2012, 178:105-117.
• [20]Schaue D, Ratikan JA, Iwamoto KS, McBride WH: Maximizing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys 2012, 83:1306-1310.
• [21]Fang Z, Yao W, Xiong Y, Zhang J, Liu L, Li J, Zhang C, Wan J: Functional elucidation and methylation-mediated downregulation of ITGA5 gene in breast cancer cell line MDA-MB-468. J Cell Biochem 2010, 110:1130-1141.
• [22]Zhang H, Xu Y, Filipovic A, Lit LC, Koo C-Y, Stebbing J, Giamas G: SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1. Br J Cancer 2013, 109:2675-2684.
• [23]Bae YK, Kim A, Kim MK, Choi JE, Kang SH, Lee SJ: Fibronectin expression in carcinoma cells correlates with tumor aggressiveness and poor clinical outcome in patients with invasive breast cancer. Hum Pathol 2013, 44:2028-2037.
• [24]Jerhammar F, Ceder R, Garvin S, Grénman R, Grafström RC, Roberg K: Fibronectin 1 is a potential biomarker for radioresistance in head and neck squamous cell carcinoma. Cancer Biol Ther 2010, 10:1244-1251.
• [25]Park S, Ahn J-Y, Lim M-J, Kim M-H, Yun Y-S, Jeong G, Song J-Y: Sustained expression of NADPH oxidase 4 by p38 MAPK-Akt signaling potentiates radiation-induced differentiation of lung fibroblasts. J Mol Med Berl Ger 2010, 88:807-816.
• [26]Cordes N, Blaese MA, Plasswilm L, Rodemann HP, Van Beuningen D: Fibronectin and laminin increase resistance to ionizing radiation and the cytotoxic drug Ukrain in human tumour and normal cells in vitro. Int J Radiat Biol 2003, 79:709-720.
• [27]Crisa L, Cirulli V, Ellisman MH, Ishii JK, Elices MJ, Salomon DR: Cell adhesion and migration are regulated at distinct stages of thymic T cell development: the roles of fibronectin, VLA4, and VLA5. J Exp Med 1996, 184:215-228.
• [28]Li X, Qian H, Ono F, Tsuchisaka A, Krol RP, Ohara K, Hayakawa T, Matsueda S, Sasada T, Ohata C, Furumura M, Hamada T, Hashimoto T: Human dermal fibroblast migration induced by fibronectin in autocrine and paracrine manners. Exp Dermatol 2014, 23:682-684.
• [29]Yokoi H, Mukoyama M, Sugawara A, Mori K, Nagae T, Makino H, Suganami T, Yahata K, Fujinaga Y, Tanaka I, Nakao K: Role of connective tissue growth factor in fibronectin expression and tubulointerstitial fibrosis. Am J Physiol Renal Physiol 2002, 282:F933-F942.
• [30]Yousif NG: Fibronectin promotes migration and invasion of ovarian cancer cells through up-regulation of FAK-PI3K/Akt pathway. Cell Biol Int 2014, 38:85-91.
• [31]Wolf M, Clark-Lewis I, Buri C, Langen H, Lis M, Mazzucchelli L: Cathepsin D specifically cleaves the chemokines macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, and SLC that are expressed in human breast cancer. Am J Pathol 2003, 162:1183-1190.
• [32]Benes P, Vetvicka V, Fusek M: Cathepsin D–many functions of one aspartic protease. Crit Rev Oncol Hematol 2008, 68:12-28.
• [33]Masson O, Bach A-S, Derocq D, Prébois C, Laurent-Matha V, Pattingre S, Liaudet-Coopman E: Pathophysiological functions of cathepsin D: Targeting its catalytic activity versus its protein binding activity? Biochimie 2010, 92:1635-1643.
• [34]Byun H-O, Han N-K, Lee H-J, Kim K-B, Ko Y-G, Yoon G, Lee Y-S, Hong S-I, Lee J-S: Cathepsin D and eukaryotic translation elongation factor 1 as promising markers of cellular senescence. Cancer Res 2009, 69:4638-4647.
• [35]Kim Y-J, Go H, Wu H-G, Jeon YK, Park SW, Lee SH: Immunohistochemical study identifying prognostic biomolecular markers in nasopharyngeal carcinoma treated by radiotherapy. Head Neck 2011, 33:1458-1466.
• [36]Desgrosellier JS, Cheresh DA: Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 2010, 10:9-22.
• [37]Lee K-M, Han W, Kim JB, Shin I, Ko E, Park IA, Lee DS, Oh K, Noh D-Y: The CD49d+/high subpopulation from isolated human breast sarcoma spheres possesses tumor-initiating ability. Int J Oncol 2012, 40:665-672.
• [38]Zucchetto A, Caldana C, Benedetti D, Tissino E, Rossi FM, Hutterer E, Pozzo F, Bomben R, Dal Bo M, D’Arena G, Zaja F, Pozzato G, Di Raimondo F, Hartmann TN, Rossi D, Gaidano G, Del Poeta G, Gattei V: CD49d is overexpressed by trisomy 12 chronic lymphocytic leukemia cells: evidence for a methylation-dependent regulation mechanism. Blood 2013, 122:3317-3321.
• [39]Marhaba R, Zöller M: CD44 in cancer progression: adhesion, migration and growth regulation. J Mol Histol 2004, 35:211-231.
• [40]Sneath RJ, Mangham DC: The normal structure and function of CD44 and its role in neoplasia. Mol Pathol MP 1998, 51:191-200.
• [41]Litwin M, Nowak D, Mazur AJ, Baczyńska D, Mannherz HG, Malicka-Błaszkiewicz M: Gelsolin affects the migratory ability of human colon adenocarcinoma and melanoma cells. Life Sci 2012, 90:851-861.
• [42]Engelholm LH, Ingvarsen S, Jürgensen HJ, Hillig T, Madsen DH, Nielsen BS, Behrendt N: The collagen receptor uPARAP/Endo180. Front Biosci Landmark Ed 2009, 14:2103-2114.
• [43]Palmieri C, Caley MP, Purshouse K, Fonseca A-V, Rodriguez-Teja M, Kogianni G, Woodley L, Odendaal J, Elliott K, Waxman J, Sturge J: Endo180 modulation by bisphosphonates and diagnostic accuracy in metastatic breast cancer. Br J Cancer 2013, 108:163-169.
• [44]Binder BR, Mihaly J, Prager GW: uPAR-uPA-PAI-1 interactions and signaling: a vascular biologist’s view. Thromb Haemost 2007, 97:336-342.
• [45]Booth NA: Fibrinolysis and thrombosis. Baillières Best Pract Res Clin Haematol 1999, 12:423-433.
• [46]Mazar AP, Henkin J, Goldfarb RH: The urokinase plasminogen activator system in cancer: implications for tumor angiogenesis and metastasis. Angiogenesis 1999, 3:15-32.
• [47]Moustakas A, Heldin P: TGFβ and matrix-regulated epithelial to mesenchymal transition. Biochim Biophys Acta 2014, 1840:2621-2634.
• [48]Oh SA, Li MO: TGF-β: guardian of T cell function. J Immunol Baltim Md 1950 2013, 191:3973-3979.
• [49]Principe DR, Doll JA, Bauer J, Jung B, Munshi HG, Bartholin L, Pasche B, Lee C, Grippo PJ: TGF-β: duality of function between tumor prevention and carcinogenesis. J Natl Cancer Inst 2014, 106:djt369.
• [50]Mocellin S, Panelli MC, Wang E, Nagorsen D, Marincola FM: The dual role of IL-10. Trends Immunol 2003, 24:36-43.
• [51]Wang Y, Liu X-H, Li Y-H, Li O: The paradox of IL-10-mediated modulation in cervical cancer. Biomed Rep 2013, 1:347-351.
• [52]De Bacco F, Luraghi P, Medico E, Reato G, Girolami F, Perera T, Gabriele P, Comoglio PM, Boccaccio C: Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer. J Natl Cancer Inst 2011, 103:645-661.
• [53]Ohuchida K, Mizumoto K, Murakami M, Qian L-W, Sato N, Nagai E, Matsumoto K, Nakamura T, Tanaka M: Radiation to stromal fibroblasts increases invasiveness of pancreatic cancer cells through tumor-stromal interactions. Cancer Res 2004, 64:3215-3222.
• [54]Park C-M, Park M-J, Kwak H-J, Lee H-C, Kim M-S, Lee S-H, Park I-C, Rhee CH, Hong S-I: Ionizing radiation enhances matrix metalloproteinase-2 secretion and invasion of glioma cells through Src/epidermal growth factor receptor-mediated p38/Akt and phosphatidylinositol 3-kinase/Akt signaling pathways. Cancer Res 2006, 66:8511-8519.
• [55]Rofstad EK, Mathiesen B, Galappathi K: Increased metastatic dissemination in human melanoma xenografts after subcurative radiation treatment: radiation-induced increase in fraction of hypoxic cells and hypoxia-induced up-regulation of urokinase-type plasminogen activator receptor. Cancer Res 2004, 64:13-18.
• [56]Kaliski A, Maggiorella L, Cengel KA, Mathe D, Rouffiac V, Opolon P, Lassau N, Bourhis J, Deutsch E: Angiogenesis and tumor growth inhibition by a matrix metalloproteinase inhibitor targeting radiation-induced invasion. Mol Cancer Ther 2005, 4:1717-1728.
• [57]Speake WJ, Dean RA, Kumar A, Morris TM, Scholefield JH, Watson SA: Radiation induced MMP expression from rectal cancer is short lived but contributes to in vitro invasion. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol 2005, 31:869-874.
• [58]Wang JL, Sun Y, Wu S: Gamma-irradiation induces matrix metalloproteinase II expression in a p53-dependent manner. Mol Carcinog 2000, 27:252-258.