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The phenotype of peripheral blood neutrophils during the early stage of endometrial cancer

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Abstract

Peripheral blood neutrophils of 123 patients in stage Ia of the endometrial cancer have been assayed. The receptor system and ability of neutrophils to form extracellular traps (NET activity) were assessed by fluorescence microscopy, and spontaneous production of IL-2, IFN-γ, matrix metalloproteinase (MMP), G-CSF was found to exist determined with enzyme-linked immunosorbent assay. Phagocytic and myeloperoxidase activity, the level of cationic proteins, and neutrophil activity were evaluated in an NBT test determining the oxygen-dependent bactericidal action of neutrophils. Topology and rigidity of neutrophil membranes were assessed using scanning probe microscopy. It was established that an increased number of neutrophils was accompanied by changes of their receptor system, aerobic and anaerobic cytotoxicity, enhanced phagocytic activity, and reduced NET activity. The secretory activity of neutrophils changed. An increased level of MMP-1, possibly by enhanced production of reactive oxygen species, reduced IL-2 level, and a drastic increase in G-CSF were observed. The architectonics of neutrophils at stage Ia of endometrial cancer was characterized by altered cell shape and granularity loss. The rigidity of the cell membrane decreased. The changes in neutrophil morphology and persistent hyperactivity suggest the existence of the equilibrium between the immune system and the tumor in stage Ia of endometrial cancer.

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Abbreviations

ROS:

reactive oxygen species

ICP:

index of completeness of phagocytosis

MMP:

matrix metalloproteinase

MPO:

myeloperoxidase

NBT:

nitroblue tetrazolium

EC:

endometrial cancer

ACC:

average cytochemical coefficient

G-CSF:

granulocyte colony stimulating factor

INF:

interferon, IL-interleukin

NET:

neutrophil extracellular traps

References

  • Ala-aho, R. and Kahari, V.-M., Collagenases in cancer, Biochimie, 2005, vol. 87, pp. 273–286.

    Article  CAS  PubMed  Google Scholar 

  • Antoneeva, I.I. and Gening, T.P., Neutrophil granulocytes in the dynamics of progression of ovarian cancer, Klin. Lab. Diagnost., 2007, vol. 8, pp. 43–46.

    Google Scholar 

  • Bakhman, Ya.V., Rukovodstvo po onkoginekologii (Manual of Gynecologic Oncology), St. Petersburg: Foliant, 2002.

    Google Scholar 

  • Berliner, N., Hsing, A., Graubert, T., Sigurdsson, F., Zain, M., Bruno, E., and Hoffman, R., Granulocyte colony-stimulating factor induction of normal human bone marrow progenitors results in neutrophil-specific gene expression, Blood, 1995, vol. 85, pp. 799–803.

    CAS  PubMed  Google Scholar 

  • Borregaard, N., Sorensen, O.E., and TheilgaardMonch, K., Neutrophil granules: a library of innate immunity proteins, Trends Immunol., 2007, vol. 28, pp. 340–345.

    Article  CAS  PubMed  Google Scholar 

  • Brandau, S., Dumitru, C.A., and Lang, S., Protumor and antitumor functions of neutrophil granulocytes, Semin. Immunopathol. Germany, 2013, vol. 35, pp. 163–176.

    Article  CAS  Google Scholar 

  • Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D.S., Weinrauch, Y., and Zychlinsky, A., Neutrophil extracellular trapskill bacteria, Science, 2004, vol. 303, pp. 1532–1535.

    Article  CAS  PubMed  Google Scholar 

  • Burlaka, A.P., Sidorik, E.P., Ganusevich, I.I., Lestchenko, Y.M., Burlaka, A.A., and Osinsky, S.P., High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels, Exp. Oncol., 2006, vol. 28, pp. 323–325.

    CAS  PubMed  Google Scholar 

  • Cools-Lartigue, J., Spicer, J., McDonald, B., Gowing, S., Chow, S., Giannias, B., Bourdeau, F., Kubes, P., and Ferri, L., Neutrophil extracellular traps sequester circulating tumor cells and promotemetastasis, J. Clin. Invest., 2013, PII. 67484.

    Google Scholar 

  • Cross, S.E., Jin, Y.S., Rao, J., and Gimzewski, J.K., Nanomechanic analysis of cells from cancer patients, Nat. Nanotechnol., 2007, vol. 2, pp. 780–783.

    Article  CAS  PubMed  Google Scholar 

  • Dallegri, F., Ottonello, L., Ballestrero, A., Dapino, P., Ferrando, F., Patrone, F., and Sacchetti, C., Tumor cell lysis by activated human neutrophils: analysis of neutrophil-delivered oxidative attack and role of leukocyte function-associated antigen 1, Inflammation, 1991, vol. 15, pp. 15–30.

    Article  CAS  PubMed  Google Scholar 

  • Davidson, B., Reich, R., Risberg, B., and Nesland, J.M., The biological role and regulation of matrix metalloproteinases (MMP) in cancer, Arkh. Patol., 2002, vol. 64, pp. 47–53.

    CAS  PubMed  Google Scholar 

  • Davydov, M.I. and Aksel, E.M., Statistika Zlokachestvennykh Novoobrazovany v Rossii i Stranakh SNG v 2012 g (Cancer Statistics in Russia and the CIS in 2012), Moscow: Izdat. Gruppa RONTs, 2014.

    Google Scholar 

  • De Oliveira-Junior, E.B., Bustamante, J., Newburger, P.E., and Condino-Neto, A., The human NADPH oxidase: primary and secondary defects impairing the respiratory burst function and the microbicidal ability of phagocytes, Scand. J. Immunol., 2011, vol. 73, pp. 420–742.

    Article  PubMed  Google Scholar 

  • Dolgushin, I.I., Shishkova, Yu.S., Semenova, A.B., Kazachkov, E.L., Vazhenin, A.V., Shamanova, A.Yu., and Dimov, G.P., A look at the role of neutrophil extracellular DNA, as a component of the tumor microenvironment, in the process of carcinogenesis, Ural. Med. Zh., 2014, vol. 2, no. 116, pp. 19–22.

    Google Scholar 

  • Dumitru, C.A., Gholaman, H., Trellakis, S., Bruderek, K., Dominas, N., Gu, X., Bankfalvi, A., Whiteside, TL, Lang, S., and Brandau, S., Tumor-derived macrophage migration inhibitory factor modulates the biology of head and neck cancer cells via neutrophil activation, Int. J. Cancer, 2011, vol. 129, pp. 859–869.

    Article  CAS  PubMed  Google Scholar 

  • Egeblad, M. and Werb, Z., New functions for the matrix metalloproteinases in cancer progression, Nat. Rev. Cancer, 2002, vol. 2, pp. 161–714.

    Article  CAS  PubMed  Google Scholar 

  • Ferlay, J., Steliarova-Foucher, E., Lortet-Tieulent, J., Rosso, S., Coebergh, J.W., Comber, H., Forman, D., and Bray, F., Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012, Eur. J. Cancer, 2013, vol. 49, pp. 1374–1403.

    Article  CAS  PubMed  Google Scholar 

  • Fingleton, B., Matrix metalloproteinases: roles in cancer and metastasis, Front. Biosci., 2006, vol. 11, pp. 479–491.

    Article  CAS  PubMed  Google Scholar 

  • Fletcher, D.A. and Mullins, R.D., Cell mechanics and the cytoskeleton, Nature, 2010, vol. 463, pp. 485–492.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fridlender, Z.G., Sun, J., Kim, S., Kapoor, V., Cheng, G., Ling, L., Worthen, G.S., and Albelda, S.M., Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN, Cancer Cell, 2009, vol. 16, pp. 183–194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ganusevich, I.I., The role of matrix metalloproteinases (MMP) in malignant tumors. I. Characterization of MMP, regulation of their activity, prognostic value, Onkologiya, 2010, vol. 12, no. 1, pp. 10–16.

    Google Scholar 

  • Gening, T.P., Abakumova, T.V., Arslanova, D.R., Voronova, O.S., Gening, S.O., and Kostishko, B.B., Morphofunctional state of human neutrophils at influence of femtosecond laser radiation in vitro, Izvestiya VUZov. Povolzh. Reg., 2011, vol. 3, pp. 3–16.

    Google Scholar 

  • Halazun, K.J., Hardy, M.A., Rana, A.A., Woodland, D.C., Luyten, E.J., Mahadev, S., Witkowski, P., Siegel, A.B., Brown, R.S., Jr., and Emond, J.C., Negative Impact of neutrophil–lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma, Ann. Surg., 2009, vol. 250, pp. 141–151.

    Article  PubMed  Google Scholar 

  • He, J.R., Shen, G.P., Ren, Z.F., Qin, H., Cui, C., Zhang, Y., Zeng, Y.X., and Jia, W.H., Pretreatment levels of peripheral neutrophils and lymphocytes as independent prognostic factors in patients with nasopharyngeal carcinoma, Head Neck, 2012, vol. 34, pp. 1769–1776.

    Article  PubMed  Google Scholar 

  • Johansson, N., Ahonen, M., and Kähäri, V.M., Matrix metalloproteinases in tumor invasion, Cell Mol. Life Sci., 2000, vol. 57, pp. 5–15.

    Article  CAS  PubMed  Google Scholar 

  • Klink, M., Jastrzembska, K., Nowak, M., Bednarska, K., Szpakowski, M., Szyllo, K., and Sulowska, Z., Ovarian cancer cells modulate human blood neutrophils response to activation in vitro, Scand. J. Immunol., 2008, vol. 68, pp. 328–336.

    Article  CAS  PubMed  Google Scholar 

  • Kuang, D.M., Zhao, Q., Wu, Y., Peng, C., Wang, J., Xu, Z., Yin, X.Y., and Zheng, L., Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma, J. Hepatol., 2011, vol. 54, pp. 948–955.

    Article  CAS  PubMed  Google Scholar 

  • Lee, K.J., Hwang, S.J., Choi, J.H., and Jeong, H.G., Saponins derived from the roots of platycodon grandiflorum inhibit HT-1080 cell invasion and MMPs activities: regulation of NF-kappaB activation via ROS signal pathway, Cancer Lett., 2008, vol. 268, pp. 233–243.

    Article  CAS  PubMed  Google Scholar 

  • Maltseva, V.N. and Safronova, V.G., The ambiguity of the role of neutrophils in the genesis of tumors, Tsitologiya, 2009, vol. 51, no. 6, pp. 467–474.

    CAS  Google Scholar 

  • Masson, V., de, la, Ballina, L.R., Munaut, C., Wielockx, B., Jost, M., Maillard, C., Blacher, S., Bajou, K., Itoh, T., Itohara, S., Werb, Z., Libert, C., Foidart, J.M., and Noël, A., Contribution of host MMP-2 and MMP-9 to promote tumor vascularization and invasion of malignant keratinocytes, FASEB J., 2005, vol. 19, pp. 234–236.

    CAS  PubMed  Google Scholar 

  • Navajas, D., Nanomechanics of Living Cells, Book of Abstracts IV Spanish Portuguese Biophysical Congress, Spain, 2010, p. 33.

    Google Scholar 

  • Nesterova, I.V., Kolesnikova, N.V., and Kovaleva, S.V., Remodeling phenotype of neutrophil granulocytes of patients with colorectal cancer under the influence of recombinant human granulocyte colony stimulating factor (G-CSF), Tsitokiny Vospalenie, 2012, vol. 11, no. 3, pp. 21–26.

    Google Scholar 

  • Nesterova, I.V., Kolesnikova, N.V., Kleschenko, E.I., Chudilova, G.A., Lomtatidze, L.V., Smerchinskaya, T.V., Sapun, O.I., and Storozhuk, S.V., Variants of transformation of the phenotype of neutrophil granulocytes CD64+CD32+CD11b+ in newborns with various infectious and inflammatory diseases, Tsitokiny Vospalenie, 2011, vol. 10, no. 4, pp. 61–65.

    Google Scholar 

  • Nesterova, I.V., Kovaleva, S.V., Chudilova, G.A., Lomtatidze, L.V., Kokov, E.A., and Storozhuk, S.V., Features of the phenotype transformation of neutrophil granulocyte subpopulations CD64(–) CD32(+) CD16(+) CD11b(+) and CDb64(+) CD32(+) CD16(+) CD11b(+) of patients with colorectal cancer under the influence of GCSF, IFN-alpha and IFN-gamma in vitro, Allergol. Immunol., 2011, vol. 12, no. 3, pp. 256–268.

    Google Scholar 

  • Nozawa, H., Chiu, C., and Hanahan, D., Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis, Proc. Natl. Acad. Sci. U. S. A., 2006, vol. 103, pp. 12493–12498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pickaver, A.H., Ratcliffe, N.A., Williams, A.E., and Smith, H., Cytotoxic effects of peritoneal neutrophils on a syngeneic rat tumour, Nat. New Biol., 1972, vol. 235, pp. 186–187.

    Article  CAS  PubMed  Google Scholar 

  • Pisareva, L.F., Boyarkina, A.P., Odintsova, I.N., and Kantorova, A.A., Epidemiological situation of uterine body cancer in the region of Siberia and the Far East. The state of cancer services. Ways of prevention, Sib. Onkol. Zh. Suppl., 2007, pp. 77–80.

    Google Scholar 

  • Pleskova, S.N., Guschina, Yu.Yu., Zvonkova, M.B., and Khomutov, A.E., Study of morphology and rigidity of neutrophilic granulocyte membrane in the real time mode by scanning probe microscopy, Bull. Exp. Biol. Med., 2006, vol. 141, no. 6, pp. 712–714.

    Article  Google Scholar 

  • Podosinnikov, I.V., Nilova, L.G., and Babichev, I.V., Method of determining the chemotactic activity of leukocytes, Lab. Delo, 1981, vol. 8, pp. 68–70.

    Google Scholar 

  • Roca-Cusachs, P., Almendros, I., Sunyer, R., Gavara, N., Farré, R., and Navajas, D., Rheology of passive and adhesion-activated neutrophils probed by atomic force microscopy, Biophys. J., 2006, vol. 91, pp. 3508–3518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rotondo, R., Barisione, G., Mastracci, L., Grossi, F., Orengo, A.M., Costa, R., Truini, M., Fabbi, M., Ferrini, S., and Barbieri, O., IL- 8 induces exocytosis of arginase 1 by neutrophil polymorphonuclears in nonsmall cell lung cancer, Int. J. Cancer, 2009, vol. 125, pp. 887–893.

    Article  CAS  PubMed  Google Scholar 

  • Rudik, D.V. and Tikhomirova, E.I., Metody izucheniya protsessa fagotsitoza i funktsional’no-metabolicheskogo sostoyaniya fagotsitiruyuschikh kletok (Methods for Studying the Process of Phagocytosis and Functional and Metabolic State of Phagocytic Cells), Saratov: Izd. Saratov. Univ., 2006.

    Google Scholar 

  • Sangaletti, S., Tripodo, C., Vitali, C., Portararo, P., Guarnotta, C., Casalini, P., Cappetti, B., Miotti, S., Pinciroli, P., Fuligni, F., Fais, F., Piccaluga, P.P., and Colombo, M.P., Defective stromal remodeling and neutrophil extracellular traps in lymphoid tissues favor the transition from autoimmunity to lymphoma, Cancer Discov. United States, 2014, vol. 4, pp. 110–129.

    Article  CAS  Google Scholar 

  • Schmidt, H., Bastholt, L., Geertsen, P., Christensen, I.J., Larsen, S., Gehl, J., and von der Maase, H., Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model, Br. J. Cancer, 2005, vol. 93, pp. 273–278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shin, M.H., Moon, Y.J., Seo, J.E., Lee, Y., Kim, K.H., and Chung, J.H., Reactive oxygen species produced by NADPH oxidase, xanthine oxidase, and mitochondrial electron transport system mediate heat shock-induced MMP-1 and MMP-9 expression, Free Rad. Biol. Med., 2008, vol. 44, pp. 635–645.

    Article  CAS  PubMed  Google Scholar 

  • Swann, J.B. and Smyth, M.J., Immune surveillance of tumors, J. Clin. Invest., 2007, vol. 117, pp. 1137–1146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wartha, F. and Henriques-Normark, B.E., Tosis: a novel cell death pathway, Sci. Signal. US, 2008, vol. 1, pp. 25.

    Google Scholar 

  • Zitvogel, L., Tesniere, A., and Kroemer, G., Cancer despite immunosurveillance: immunoselection and immunosubversion, Nat. Rev. Immunol., 2006, vol. 6, pp. 715–727.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Ulyanovsk State University, Ulyanovsk, 432017, Russia

    T. V. Abakumova, I. I. Antoneeva, T. P. Gening, D. R. Dolgova & S. O. Gening

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  1. T. V. Abakumova
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  2. I. I. Antoneeva
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  3. T. P. Gening
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  4. D. R. Dolgova
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  5. S. O. Gening
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Correspondence to T. V. Abakumova.

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Original Russian Text © T.V. Abakumova, I.I. Antoneeva, T.P. Gening, D.R. Dolgova, S.O. Gening, 2016, published in Tsitologiya, 2016, Vol. 58, No. 1, pp. 23–29.

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Abakumova, T.V., Antoneeva, I.I., Gening, T.P. et al. The phenotype of peripheral blood neutrophils during the early stage of endometrial cancer. Cell Tiss. Biol. 10, 206–212 (2016). https://doi.org/10.1134/S1990519X16030020

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