Abstract
Electron paramagnetic resonance (EPR) experiments in vitro; spin trapping of the reactive oxygen/nitrogen species (superoxide radicals and nitric oxide, NO); gel zymography measurements in the tumor tissues, in the healthy and tumor-affected bone marrow (BM) samples of rats are carried out. The superoxide and NO generation rates are derived; matrix metalloproteinases (MMP-2 and MMP-9) concentrations are measured. Their changes after the incubation of BM samples with Guérin carcinoma cells at 37 °C are defined. It is shown that the impact of tumor cells on BM manifests in the metabolic disorder, increased concentrations of active forms of MMP-2 and MMP-9, increased production of superoxide and NO radicals. Correlation between the appearance and intensity of the broad EPR signal at g = 2.2–2.4 with the concentrations of active forms of MMP-2 and MMP-9, NO and superoxide radicals’ rates is observed. The obtained spatial and temporal changes of the measured parameters demonstrate the usefulness of the potential application of EPR imaging to study the mechanisms of tumor invasion. The EPR signal may indicate the presence of distant metastases, may become a part of diagnostics and used for the estimation of the therapeutic treatments in the pre-clinical studies. It is proposed that labile iron pool is responsible for the appearance of the EPR signal in tumor and BM samples.
Similar content being viewed by others
References
S.K. Biswas, Tumor Microenvironment and Myelomonocytic Cells (InTech, Rijeka, 2012), p. 1
L.M. Bystrom, M.L. Guzman, S. Rivella, Antioxid. Redox Sign. 20, 1917 (2014)
S.V. Torti, F.M. Torti, Nat. Rev. Cancer 13, 342 (2013)
R.L. Elliott, J.F. Head, J. Cancer Ther. 3, 278 (2012)
V. Srinivasan, D.W. Spence, S.R. Pandi-Perumal, G.M. Brown, D.P. Cardinali, Int. J. Alzheimer’s Dis. 2011, 326320 (2011)
F. Sotgia, U.E. Martinez-Outschoorn, M.P. Lisanti, BMC Med. 9, 1741 (2011)
D. Hanahan, R.A. Weinberg, Cell 100, 57 (2000)
C. Gialeli, A.D. Theocharis, N.K. Karamanos, FEBS 278, 16 (2011)
U.B. Hoffman, A.A. Eggert, K. Blass, E.B. Bröcker, J.C. Becker, Cancer Res. 63, 8221 (2003)
A.P. Burlaka, E.P. Sidorik, I.I. Ganusevich, S.P. Osinsky, Exp. Oncol. 28, 49 (2006)
A.P. Burlaka, E.P. Sidorik, I.I. Ganusevich, Y.M. Leschenko, S.P. Osinsky, Exp. Oncol. 28, 323 (2006)
A.P. Burlaka, E.P. Sidorik, Radical Forms of Oxygen and Nitrogen Oxide in the Tumors Process (Naukova dumka, Kiev, 2006), p. 1. (in Ukrainian)
J.B. Kim, R. Stein, M.J. O’Hare, Tumor Biol. 26, 173 (2005)
A.P. Burlaka, I.I. Ganusevich, M.R. Gafurov, S.N. Lukin, E.P. Sidorik, Cancer Microenviron. 6, 273 (2013)
A. Burlaka, M. Selyuk, M. Gafurov, S. Lukin, V. Potaskalova, E. Sidorik, e. Int. J. Rad. Biol. 90, 357 (2014)
Z.P. Sofyina, A.B. Syrkin, A. Goldin, A. Klein, Evaluation of Antitumor Drugs in the USSR and USA (Medicine, Moscow, 1980), p. 1. (in Russian)
J.R. Mallard, M. Kent, Phys. Med. Biol. 14, 373 (1969)
N.M. Emanuel, R.E. Kavetskii, B.N. Tarusov, E.P. Sidorik, Cancer Biophysics (Naukova dumka, Kiev, 1976), p. 1. (in Russian)
J.I. Azhipa, Medical-Biological Aspects in Electron Paramagnetic Resonance Method Applications (Nauka, Moscow, 1983), p. 1. (in Russian)
M.K. Pulatova, G.T. Rikhireva, Z.V. Kuropteva, Electron Spin Resonance in Molecular Radiobiology (Energoatomizdat, Moscow, 1989), p. 1. (in Russian)
R.G. Saifutdinov, L.I. Larina, T.I. Vakul’skaya, M.G. Voronkov, Electron Paramagnetic Resonance in Biochemistry and Medicine (Springer, New York, 2001). 1
S.S. Eaton, G.R. Eaton, L.J. Berliner, Biomedical EPR: Part A: Free Radicals, Metals, Medicine and Physiology (Springer, New York, 2005), p. 1
S.S. Eaton, G.R. Eaton, L.J. Berliner, Biomedical EPR: Part B: Methodology, Instrumentation, and Dynamics (Springer, New York, 2005), p. 1
W.R. Hagen, Biomolecular EPR Spectroscopy (CRC Press, Boca Raton, 2009), p. 1
G. Hanson, L. Berliner, High Resolution EPR. Applications to Metalloenzymes and Metals in Medicine (Springer, New York, 2009), p. 1
L.A. Krinitskaya, L.B. Volodarskii, Russ. Chem. Bull. 31, 401 (1982)
S. Dikalov, M. Skatchkov, E. Bassenge, Biochem. Biophys. Res. Commun. 230, 54 (1997)
A. Mülsch, P. Mordvintcev, A. Vanin, Neuroprotocols 1, 165 (1992)
R. Fridman, T.R. Fuerst, R.E. Bird, M. Hoyhtya, M. Oelkuct, S. Kraus, D. Komarek, L.A. Liotta, M.L. Berman, W.G. Stetler-Stevenson, J. Biol. Chem. 267, 15398 (1992)
M. Toth, A. Sohail, R. Fridman, in Metastasis Research Protocols Methods in Molecular Biology, vol. 878, ed. by M. Dwek, S.A. Briiks (Springer, New York, 2012), p. 121
N.M. Emanuel, Pure Appl. Chem. 52, 11 (1980)
A.A. Konstantinov, E.K. Ruuge, FEBS Lett. 181, 137 (1977)
N.M. Emanuel, A.N. Saprin, V.A. Shabalkin, L.E. Kozlova, K.E. Krugljakova, Nature 222, 165 (1965)
S.A. Altshuler, B.M. Kozyrev, Electron Paramagnetic Resonance in Compounds of Transition Elements, 2nd edn. (Nauka, Moscow, 1972), pp. 380–549. (in Russian)
S.V. Yurtaeva, V.N. Efimov, N.I. Silkin, A.A. Rodionov, M.V. Burmistrov, A.V. Panov, A.A. Moroshek, Appl. Magn. Reson. 42, 299 (2012)
A. Albini, M.B. Sporn, Nat. Rev. Cancer 7, 139 (2007)
M. Arredondo, M.T. Nunez, Mol. Aspects Med. 26, 313 (2005)
B.V. Yavkin, G.V. Mamin, S.B. Orlinskii, M.R. Gafurov, M.K. Salakhov, T.B. Biktagirov, E.S. Klimashina, V.I. Putlayev, YuD Tretyakov, N.I. Silkin, Phys. Chem. Chem. Phys. 14, 2246 (2012)
T.B. Biktagirov, Y.A. Chelyshev, M.R. Gafurov, G.V. Mamin, S.B. Orlinskii, Y.N. Osin, M.K. Salakhov, J. Phys: Conf. Ser. 478, 012002 (2013)
M.R. Gafurov, T.B. Biktagirov, B.V. Yavkin, G.V. Mamin, Y.Y. Filippov, E.S. Klimashina, V.I. Putlayev, S.B. Orlinskii, JETP Lett. 99, 196 (2014)
L.D. Landau, E.M. Lifshitz, Fluid Mechanics, Vol. 6 of a Course of Theoretical Physics (Pergamon Press, Oxford, 1959), pp. 474–480
P. Tracqui, Rep. Prog. Phys. 72, 056701 (2009)
Acknowledgments
This work was funded by the subsidy of the Russian Government to support the Program of competitive Growth of Kazan Federal University among World’s Leading Academic Centers. We appreciate the support of Dr. Sergei Orlinskii and Dr. Georgy Mamin (Kazan) for their fruitful discussions of the results and support of the Project.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Burlaka, A.P., Ganusevich, I.I., Lukin, S.N. et al. Superoxide- and NO-Dependent Mechanisms of the Reprogramming of Bone Marrow Cells by Tumor Cells. Appl Magn Reson 45, 1261–1273 (2014). https://doi.org/10.1007/s00723-014-0610-y
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00723-014-0610-y