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Erschienen in: Tumor Biology 4/2014

01.04.2014 | Research Article

Staphylococcal entorotoxin B anchored exosome induces apoptosis in negative esterogen receptor breast cancer cells

verfasst von: Hamideh Mahmoodzadeh Hosseini, Abbas Ali Imani Fooladi, Jafar Soleimanirad, Mohammad Reza Nourani, Soodabeh Davaran, Mehdi Mahdavi

Erschienen in: Tumor Biology | Ausgabe 4/2014

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Abstract

Exosomes (EXO) are acellular vehicles used for cancer immunotherapy due to their immune inducing properties. To identify whether designed structure based on tumoral EXO have a cytotoxic effect together with a potent immunological property, we synthesized a novel structure based on EXO and staphylococcal entrotoxin B (SEB), two immune inducer substances, and surveyed its cytostatic effect on the breast cancer cell line. EXO were purified from tumor cells and SEB was anchored on it by protein transfer method. To determine the cytotoxic and apoptosis inducing effect of this structure, treated cells with different concentrations of EXO/SEB were examined by MTT assay and Hoechst staining method. In addition, the expression rate of bcl-2, bax, bak, fas, bcl-xl and the activity of caspase-3 and caspase-9 were assessed. We observed that EXO/SEB significantly decreased the cell proliferation and stimulated apoptosis (P < 0.001) at all concentration after 24 h (P < 0.001). Furthermore, EXO/SEB raised the expression rate of bax and bak (P < 0.001) but no impact on fas and bcl-xl after 48 h. We observed reducing effect of EXO/SEB on the mRNA expression of bcl-2. After 24 h of exposing the cell with the EXO/SEB, a significant increase was found in the activity of caspase at the concentration of 2.5, 5 and 10 μg/100 μl for caspase-9 and at all concentrations for caspase-3 (P < 0.001). Our designed structure, the EXO/SEB, is a novel model for apopto-immunotherapy being able to induce apoptosis in ER breast cancer cells.
Literatur
1.
Zurück zum Zitat Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.PubMedCrossRef Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.PubMedCrossRef
2.
Zurück zum Zitat Lanari C, Wargon V, Rojas P, Molinolo AA. Antiprogestins in breast cancer treatment: are we ready? Endocr Relat Cancer. 2012;19:R35–50.PubMedCrossRef Lanari C, Wargon V, Rojas P, Molinolo AA. Antiprogestins in breast cancer treatment: are we ready? Endocr Relat Cancer. 2012;19:R35–50.PubMedCrossRef
3.
Zurück zum Zitat Soto-Cerrato V, Llagostera E, Montaner B, Scheffer GL, Perez-Tomas R. Mitochondria-mediated apoptosis operating irrespective of multidrug resistance in breast cancer cells by the anticancer agent prodigiosin. Biochem Pharmacol. 2004;68:1345–52.PubMedCrossRef Soto-Cerrato V, Llagostera E, Montaner B, Scheffer GL, Perez-Tomas R. Mitochondria-mediated apoptosis operating irrespective of multidrug resistance in breast cancer cells by the anticancer agent prodigiosin. Biochem Pharmacol. 2004;68:1345–52.PubMedCrossRef
4.
Zurück zum Zitat Koido S, Homma S, Takahara A, Namiki Y, Tsukinaga S, Mitobe J, et al. Current immunotherapeutic approaches in pancreatic cancer. Clin Dev Immunol. 2011;2011:267539.PubMedCentralPubMedCrossRef Koido S, Homma S, Takahara A, Namiki Y, Tsukinaga S, Mitobe J, et al. Current immunotherapeutic approaches in pancreatic cancer. Clin Dev Immunol. 2011;2011:267539.PubMedCentralPubMedCrossRef
5.
Zurück zum Zitat Rieger J, Freichels H, Imberty A, Putaux JL, Delair T, Jérôme C, et al. Polyester nanoparticles presenting mannose residues: toward the development of new vaccine delivery systems combining biodegradability and targeting properties. Biomacromolecules. 2009;10:651–7.PubMedCrossRef Rieger J, Freichels H, Imberty A, Putaux JL, Delair T, Jérôme C, et al. Polyester nanoparticles presenting mannose residues: toward the development of new vaccine delivery systems combining biodegradability and targeting properties. Biomacromolecules. 2009;10:651–7.PubMedCrossRef
6.
Zurück zum Zitat Hosseini HM, Fooladi AA, Nourani MR, Ghanezadeh F. Role of Exosome in infectious disease. Inflamm Allergy Drug Targets. 2013;12:29–37.PubMedCrossRef Hosseini HM, Fooladi AA, Nourani MR, Ghanezadeh F. Role of Exosome in infectious disease. Inflamm Allergy Drug Targets. 2013;12:29–37.PubMedCrossRef
8.
Zurück zum Zitat Cho JA, Yeo DJ, Son HY, Kim HW, Jung DS, Ko JK, et al. Exosomes: a new delivery system for tumor antigens in cancer immunotherapy. Int J Cancer. 2005;114:613–22.PubMedCrossRef Cho JA, Yeo DJ, Son HY, Kim HW, Jung DS, Ko JK, et al. Exosomes: a new delivery system for tumor antigens in cancer immunotherapy. Int J Cancer. 2005;114:613–22.PubMedCrossRef
9.
Zurück zum Zitat Tan A, De La Peña H, Seifalian AM. The application of exosomes as a nanoscale cancer vaccine. Int J Nanomedicine. 2010;5:889–900.PubMedCentralPubMed Tan A, De La Peña H, Seifalian AM. The application of exosomes as a nanoscale cancer vaccine. Int J Nanomedicine. 2010;5:889–900.PubMedCentralPubMed
10.
Zurück zum Zitat Ristorcelli E, Beraud E, Mathieu S, Lombardo D, Verine A. Essential role of Notch signaling in apoptosis of human pancreatic tumoral cells mediated by exosomal nanoparticles. Int J Cancer. 2009;125:1016–26.PubMedCrossRef Ristorcelli E, Beraud E, Mathieu S, Lombardo D, Verine A. Essential role of Notch signaling in apoptosis of human pancreatic tumoral cells mediated by exosomal nanoparticles. Int J Cancer. 2009;125:1016–26.PubMedCrossRef
11.
Zurück zum Zitat Ristorcelli E, Beraud E, Verrando P, Villard C, Lafitte D, Sbarra V, et al. Human tumor nanoparticles induce apoptosis of pancreatic cancer cells. FASEB J. 2008;22:3358–69.PubMedCrossRef Ristorcelli E, Beraud E, Verrando P, Villard C, Lafitte D, Sbarra V, et al. Human tumor nanoparticles induce apoptosis of pancreatic cancer cells. FASEB J. 2008;22:3358–69.PubMedCrossRef
12.
Zurück zum Zitat Choi YW, Kotzin B, Herron L, Callahan J, Marrack P, Kappler J. Interaction of Staphylococcus aureus toxin “superantigens” with human T cells. Proc Natl Acad Sci. 1989;86:8941–5.PubMedCentralPubMedCrossRef Choi YW, Kotzin B, Herron L, Callahan J, Marrack P, Kappler J. Interaction of Staphylococcus aureus toxin “superantigens” with human T cells. Proc Natl Acad Sci. 1989;86:8941–5.PubMedCentralPubMedCrossRef
13.
Zurück zum Zitat Kappler J, Kotzin B, Herron L, Gelfand EW, Bigler RD, Boylston A, et al. V beta-specific stimulation of human T cells by staphylococcal toxins. Science. 1989;244:811–3.PubMedCrossRef Kappler J, Kotzin B, Herron L, Gelfand EW, Bigler RD, Boylston A, et al. V beta-specific stimulation of human T cells by staphylococcal toxins. Science. 1989;244:811–3.PubMedCrossRef
14.
Zurück zum Zitat Imani Fooladi AA, Sattari M, Hassan ZM, Mahdavi M, Azizi T, Horii A. In vivo induction of necrosis in mice fibrosarcoma via intravenous injection of type B staphylococcal enterotoxin. Biotechnol Lett. 2008;30:2053–9.CrossRef Imani Fooladi AA, Sattari M, Hassan ZM, Mahdavi M, Azizi T, Horii A. In vivo induction of necrosis in mice fibrosarcoma via intravenous injection of type B staphylococcal enterotoxin. Biotechnol Lett. 2008;30:2053–9.CrossRef
15.
Zurück zum Zitat Imani Fooladi AA, Sattari M, Nourani MR. Synergistic effects between staphylococcal enterotoxin type B and monophosphoryl lipid A against mouse fibrosarcoma. J BUON. 2010;15:7. Imani Fooladi AA, Sattari M, Nourani MR. Synergistic effects between staphylococcal enterotoxin type B and monophosphoryl lipid A against mouse fibrosarcoma. J BUON. 2010;15:7.
16.
Zurück zum Zitat Fooladi AAI, Sattari M, Nourani MR. Study of T-cell stimulation and cytokine release induced by staphylococcal enterotoxin type B and monophosphoryl lipid A. Arch Med Sci. 2009:335–41. Fooladi AAI, Sattari M, Nourani MR. Study of T-cell stimulation and cytokine release induced by staphylococcal enterotoxin type B and monophosphoryl lipid A. Arch Med Sci. 2009:335–41.
17.
Zurück zum Zitat Higgs BW, Dileo J, Chang WE, Smith HB, Peters OJ, Hammamieh R, et al. Modeling the effects of a Staphylococcal Enterotoxin B (SEB) on the apoptosis pathway. BMC Microbiol. 2006;6:48.PubMedCentralPubMedCrossRef Higgs BW, Dileo J, Chang WE, Smith HB, Peters OJ, Hammamieh R, et al. Modeling the effects of a Staphylococcal Enterotoxin B (SEB) on the apoptosis pathway. BMC Microbiol. 2006;6:48.PubMedCentralPubMedCrossRef
18.
Zurück zum Zitat Battke C, Ruiss R, Welsch U, Wimberger P, Lang S, Jochum S, et al. Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC. Cancer Immunol Immunother. 2011;60:639–48.PubMedCrossRef Battke C, Ruiss R, Welsch U, Wimberger P, Lang S, Jochum S, et al. Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC. Cancer Immunol Immunother. 2011;60:639–48.PubMedCrossRef
20.
Zurück zum Zitat McHugh RS, Nagarajan S, Wang YC, Sell KW, Selvaraj P. Protein transfer of glycosyl-phosphatidylinositol-B7-1 into tumor cell membranes: a novel approach to tumor immunotherapy. Cancer Res. 1999;59:2433–7.PubMed McHugh RS, Nagarajan S, Wang YC, Sell KW, Selvaraj P. Protein transfer of glycosyl-phosphatidylinositol-B7-1 into tumor cell membranes: a novel approach to tumor immunotherapy. Cancer Res. 1999;59:2433–7.PubMed
21.
22.
Zurück zum Zitat Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993;74:609–19.PubMedCrossRef Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993;74:609–19.PubMedCrossRef
23.
Zurück zum Zitat Devarajan E, Sahin AA, Chen JS, Krishnamurthy RR, Aggarwal N, Brun AM, et al. Down-regulation of caspase 3 in breast cancer: a possible mechanism for chemoresistance. Oncogene. 2002;21:8843–51.PubMedCrossRef Devarajan E, Sahin AA, Chen JS, Krishnamurthy RR, Aggarwal N, Brun AM, et al. Down-regulation of caspase 3 in breast cancer: a possible mechanism for chemoresistance. Oncogene. 2002;21:8843–51.PubMedCrossRef
24.
Zurück zum Zitat Fadeel B, Orrenius S. Apoptosis: a basic biological phenomenon with wide-ranging implications in human disease. J Intern Med. 2005;258:479–517.PubMedCrossRef Fadeel B, Orrenius S. Apoptosis: a basic biological phenomenon with wide-ranging implications in human disease. J Intern Med. 2005;258:479–517.PubMedCrossRef
25.
Zurück zum Zitat Sharief M, Gani ZH. Garden cress Lepidium sativum seeds as oral contraceptive plant in mice. Saudi Med J. 2004;25:965–6.PubMed Sharief M, Gani ZH. Garden cress Lepidium sativum seeds as oral contraceptive plant in mice. Saudi Med J. 2004;25:965–6.PubMed
26.
Zurück zum Zitat Ferenbach DA, Haydon GH, Rae F, Malcomson RD, Harrison DJ. Alteration in mRNA levels of Fas splice variants in hepatitis C-infected liver. J Pathol. 1997;183:299–304.PubMedCrossRef Ferenbach DA, Haydon GH, Rae F, Malcomson RD, Harrison DJ. Alteration in mRNA levels of Fas splice variants in hepatitis C-infected liver. J Pathol. 1997;183:299–304.PubMedCrossRef
27.
Zurück zum Zitat Marone M, Mozzetti S, De Ritis D, Pierelli L, Scambia G. Semiquantitative RT-PCR analysis to assess the expression levels of multiple transcripts from the same sample. Biol Proced Online. 2001;3:19–25.PubMedCentralPubMedCrossRef Marone M, Mozzetti S, De Ritis D, Pierelli L, Scambia G. Semiquantitative RT-PCR analysis to assess the expression levels of multiple transcripts from the same sample. Biol Proced Online. 2001;3:19–25.PubMedCentralPubMedCrossRef
28.
Zurück zum Zitat Chen JH, Cao JL, Chu YL, Wang ZL, Yang ZT, Wang HL. T-2 toxin-induced apoptosis involving Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 signaling pathways in human chondrocytes. J Zhejiang Univ Sci B. 2008;9(6):455–63.PubMedCentralPubMedCrossRef Chen JH, Cao JL, Chu YL, Wang ZL, Yang ZT, Wang HL. T-2 toxin-induced apoptosis involving Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 signaling pathways in human chondrocytes. J Zhejiang Univ Sci B. 2008;9(6):455–63.PubMedCentralPubMedCrossRef
29.
Zurück zum Zitat Kim H, Chung H, Kim HJ, Lee JY, Oh MY, Kim Y, et al. Id-1 regulates Bcl-2 and Bax expression through p53 and NF-kappaB in MCF-7 breast cancer cells. Breast Cancer Res Treat. 2008;112(2):287–96.PubMedCrossRef Kim H, Chung H, Kim HJ, Lee JY, Oh MY, Kim Y, et al. Id-1 regulates Bcl-2 and Bax expression through p53 and NF-kappaB in MCF-7 breast cancer cells. Breast Cancer Res Treat. 2008;112(2):287–96.PubMedCrossRef
30.
Zurück zum Zitat Banisor I, Kalman B. Bcl-2 and its homologues in the brain of patients with multiple sclerosis. Mult Scler. 2004;10(2):176–81.PubMed Banisor I, Kalman B. Bcl-2 and its homologues in the brain of patients with multiple sclerosis. Mult Scler. 2004;10(2):176–81.PubMed
31.
Zurück zum Zitat Khaheshi I, Keshavarz S, Imani Fooladi AA, Ebrahimi M, Yazdani S, Panahi Y, et al. Loss of expression of TGF-βs and their receptors in chronic skin lesions induced by sulfur mustard as compared with chronic contact dermatitis patients. BMC Dermatol. 2011;11:2.PubMedCentralPubMedCrossRef Khaheshi I, Keshavarz S, Imani Fooladi AA, Ebrahimi M, Yazdani S, Panahi Y, et al. Loss of expression of TGF-βs and their receptors in chronic skin lesions induced by sulfur mustard as compared with chronic contact dermatitis patients. BMC Dermatol. 2011;11:2.PubMedCentralPubMedCrossRef
Metadaten
Titel
Staphylococcal entorotoxin B anchored exosome induces apoptosis in negative esterogen receptor breast cancer cells
verfasst von
Hamideh Mahmoodzadeh Hosseini
Abbas Ali Imani Fooladi
Jafar Soleimanirad
Mohammad Reza Nourani
Soodabeh Davaran
Mehdi Mahdavi
Publikationsdatum
01.04.2014
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 4/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1489-1

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