Alterations in mRNA expression of rat astrocytes CO-cultured with C6 glioma cells and impact of glioma-conditioned astrocytes on dendritic cell maturation


如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅或者付费存取

详细

Introduction. Under the influence of glioma cells, peritumoral zone astrocytes may acquire tumorigenic phenotype, particularly due to the suppression of immunocompetent cells. The aim of the study. Investigate the changes in the gene expression profile of glioma-conditioned rat astrocytes and the impact of conditioned astrocyte cellular extracts (lysates) on dendritic cell maturation. Methods. We compared glioma-conditioned astrocytes with C6 glioma cells or native astrocytes. Astrocyte conditioning was achieved by indirect co-culturing of native astrocytes with C6 glioma cells. The expression profile was assessed with real-time PCR. The phenotype of dendritic cells pulsed with extracts of glioma-conditioned astrocytes, C6 glioma cells and native astrocytes was studied with flow cytometry and ELISA. Dendritic cells were also used for rat immunization. We measured serum interferon-γ dynamics and cytokine production (interferon-γ, interleukins 4 and 10) by mononuclear cells of immunized rats. Results. Conditioned astrocytes showed a tendency to upregulation of interleukin 6 mRNA. They also demonstrated lower expression of PDGFB chain mRNA. Glioma cells expressed higher levels of nestin, GFAP, and CD44 mRNA. CCL2 chemokine mRNA was expressed at lower amounts in glioma cells and glioma-conditioned astrocytes. Dendritic cells pulsed with extracts of conditioned astrocytes yielded a lower increase of serum and mononuclear-derived interferon-γ after rat immunization. These dendritic cells exposed less CD11b/c but produced more interleukin 12 in comparison. Conclusion. The findings suggest that astrocytes may undergo phenotype transformation under the influence of glioma cells and obtain traits different from glioma cells or native astrocytes and similar to both cellular types at the same time

全文:

受限制的访问

作者简介

Anastasia Chernysheva

V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, Ministry of Health of the Russian Federation

Email: aachernysheva512@gmail.com
junior researcher

Ivan Chekhonin

V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, Ministry of Health of the Russian Federation

Email: chekhonin@yandex.ru
research scientist

Anastasia Sosnovtseva

V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, Ministry of Health of the Russian Federation

Email: sollomia@yandex.ru
junior researcher

Sergey Cherepanov

V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, Ministry of Health of the Russian Federation; Pirogov Russian National Research Medical University

Email: cherep.serega@gmail.com
research scientist

Karina Kardashova

V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, Ministry of Health of the Russian Federation

Email: kksh08@yandex.ru
senior researcher

Olga Gurina

V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, Ministry of Health of the Russian Federation

Email: olga672@yandex.ru
Head of the laboratory of neurochemistry, Dr. of Medical Sciences, professor of RAS, Corresponding Member of RAS.

Artemiy Silantyev

National Scientific Research Center on Addictions - a branch of the V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, Ministry of Health of the Russian Federation

Email: artsilan@gmail.com
junior researcher

Svetlana Pavlova

Institute of Institute of Higher Nervous Activity and Neurophysiology of the Russian Federation

Email: pavlova.sweti@yandex.ru
graduate student

Galina Pavlova

Institute of Institute of Higher Nervous Activity and Neurophysiology of the Russian Federation; Sechenov First Moscow State Medical University; «N.N. Burdenko National Medical Research Center of Neurosurgery» of the Ministry of Health of the Russian Federation

Email: lkorochkin@mail.ru
Head of the laboratory; professor of RAS.

Tatiana Savelieva

Prokhorov General Physics Institute of the Russian Academy of Sciences; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)

Email: savelevat@gmail.com
research scientist

Victor Loshhenov

Prokhorov General Physics Institute of the Russian Academy of Sciences; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)

Email: loschenov@mail.ru
Head of the Laser Biospectroscopy Laboratory

Vladimir Chekhonin

V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, Ministry of Health of the Russian Federation; Pirogov Russian National Research Medical University

Email: chekhoninnew@yandex.ru
head of the Department of Fundamental and Applied Neurobiology

参考

  1. Broekman M.L., Maas S.L.N., Abels E.R., Mempel T.R., Krichevsky A.M., Breakefield X.O. Multidimensional communication in the microenvirons of glioblastoma. Nat Rev Neurol. 2018; 14 (8): 482-95. https://doi.org/10.1038/s41582-018-0025-8.
  2. Brandao M., Simon T., Critchley G., Giamas G. Astrocytes, the rising stars of the glioblastoma microenvironment. Glia. 2019; 67 (5): 779-90. https://doi.org/10.1002/glia.23520.
  3. Katz A.M., Amankulor N.M., Pitter K., Helmy K., Squatrito M., Holland E.C. Astrocyte-specific expression patterns associated with the PDGF-induced glioma microenvironment. PLoS One. 2012; 7 (2): e32453. https://doi.org/10.1371/journal.pone.0032453.
  4. Gagliano N., Costa F., Cossetti C., Pettinari L., Bassi R., Chiriva-Internati M., Cobos E., Gioia M., Pluchino S. Glioma-astrocyte interaction modifies the astrocyte phenotype in a co-culture experimental model. Oncol Rep. 2009; 22 (6): 1349-56. https://doi.org/10.3892/or_00000574.
  5. Fazi B., Felsani A., Grassi L., Moles A., D'Andrea D., Toschi N., Sicari D., De Bonis P., Anile C., Guerrisi M.G., Luca E., Farace M.G., Maira G., Ciafre S.A., Mangiola A. The transcriptome and miRNome profiling of glioblastoma tissues and peritumoral regions highlights molecular pathways shared by tumors and surrounding areas and reveals differences between shortterm and long-term survivors. Onco-target. 2015; 6 (26): 22526-52. https://doi.org/10.18632/oncotarget.4151.
  6. Liau L.M., Ashkan K., Tran D.D., Campian J.L., Trusheim J.E., Cobbs C.S., Heth J.A., Salacz M., Taylor S., D'Andre S.D., Iwamoto F.M., Dropcho E.J., Moshel Y.A., Walter K.A., Pillainayagam C.P., Aiken R., Chaudhary R., Goldlust S.A., Bota D.A., Duic P., Grewal J., Elinzano H., Toms S.A., Lillehei K.O., Mikkelsen T., Walbert T., Abram S.R., Brenner A.J., Brem S., Ewend M.G., Khagi S., Portnow J., Kim L.J., Loudon W.G., Thompson R.C., Avigan D.E., Fink K.L., Geoffroy F.J., Lindhorst S., Lutzky J., Sloan A.E., Schackert G., Krex D., Meisel H.J., Wu J., Davis R.P., Duma C., Etame A.B., Mathieu D., Kesari S., Piccioni D., Westphal M., Baskin D.S., New P.Z., Lacroix M., May S.A., Pluard T.J., Tse V., Green R.M., Villano J.L., Pearlman M., Petrecca K., Schulder M., Taylor L.P., Maida A.E., Prins R.M., Cloughesy T.F., Mulholland P., Bosch M.L. First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J. Transl Med. 2018; 16 (1): 142. https://doi.org/10.1186/s12967-018-1507-6.
  7. Fang B.J., Geng F.Y., Lu F.Q., Wang Y.H., Zhang L.Q., Meng F.G. Expression and clinical significance of nestin in astrocytic tumors. J. buon. 2016; 21 (1): 191-8.
  8. McFarland B.C., Hong S.W., Rajbhandari R., Twitty G.B., Jr., Gray G.K., Yu H., Benveniste E.N., Nozell S.E. NF-KB-induced IL6 ensures STAT3 activation and tumor aggressiveness in glioblastoma. PLoS One. 2013; 8 (11): e78728. https://doi.org/10.1371/journal.pone.0078728.
  9. Baklaushev V.P, Yusubalieva G.M., Tsitrin E.B., Gurina O.I., Grinenko N.P, Victorov I.V, Chekhonin V.P. Visualization of Connexin 43-positive cells of glioma and the periglioma zone by means of intravenously injected monoclonal antibodies. Drug Deliv. 2011; 18 (5): 331-7. https://doi.org/10.3109/10717544.2010.549527
  10. Westermark B. Platelet-derived growth factor in glioblastoma-driver or biomarker? Ups J. Med. Sci. 2014; 119 (4): 298-305. https://doi.org/10.3109/03009734.2014.970304
  11. Chekhonin I.V, Gurina O.I., Cherepanov S.A., Abakumov M.A., Ionova K.P, Zhigarev D.I., Makarov A.V., Chekhonin V.P Pulsed Dendritic Cells for the Therapy of Experimental Glioma. Bull Exp. Biol. Med. 2016; 161 (6): 792-6. https://doi.org/10.1007/s10517-016-3512-1
  12. Jiang Y., Han S., Cheng W., Wang Z., Wu A. NFAT1-regulated IL6 signalling contributes to aggressive phenotypes of glioma. Cell Commun Signal. 2017; 15 (1): 54. https://doi.org/10.1186/s12964-017-0210-1.
  13. Funa K., Sasahara M. The roles of PDGF in development and during neurogenesis in the normal and diseased nervous system. J. Neuroimmune Pharmacol. 2014; 9 (2): 168-81. https://doi.org/10.1007/s11481-013-9479-z.
  14. Mauro A., Bulfone A., Turco E., Schiffer D. Coexpression of platelet-derived growth factor (PDGF) B. chain and PDGF B-type receptor in human gliomas. Childs Nerv Syst. 1991; 7 (8): 432-6. https://doi.org/10.1007/ BF00263184.
  15. Chekhonin V.P, Baklaushev V.P, Yusubalieva G.M., Belorusova A.E., Gulyaev M.V., Tsitrin E.B., Grinenko N.F., Gurina O.I., Pirogov YA. Targeted delivery of liposomal nanocontainers to the peritumoral zone of glioma by means of monoclonal antibodies against GFAP and the extracellular loop of Cx43. Nanomedicine. 2012; 8 (1): 63-70. https://doi.org/10.10Wj.nano.2011.05.011
  16. Vogel C., Marcotte E.M. Insights into the regulation of protein abundance from pro-teomic and transcriptomic analyses. Nat Rev Genet. 2012; 13 (4): 227-32. https://doi.org/10.1038/nrg3185.
  17. Van Bodegraven E.J., van Asperen J.V., Robe P.A.J., Hol E.M. Importance of GFAP isoform-specific analyses in astrocytoma. Glia. 2019; 67 (8): 1417-33. https://doi.org/10.1002/glia.23594.
  18. Wang H.H., Liao C.C., Chow N.H., Huang L.L., Chuang J.I., Wei K.C., Shin J.W. Whether CD44 is an applicable marker for glioma stem cells. Am. J. Transl. Res. 2017; 9 (11): 4785-806.
  19. Chang A.L., Miska J., Wainwright D.A., Dey M., Rivetta C.V., Yu D., Kanojia D., Pituch K.C., Qiao J., Pytel P., Han Y., Wu M., Zhang L., Horbinski C.M., Ahmed A.U., Lesniak M.S. CCL2 Produced by the Glioma Microenvironment Is Essential for the Recruitment of Regulatory T. Cells and Myeloid-Derived Suppressor Cells. Cancer Res. 2016; 76 (19): 5671-82. https://doi.org/10.1158/0008-5472.Can-16-0144.
  20. Leung S.Y., Wong M.P., Chung L.P., Chan A.S., Yuen S.T. Monocyte chemoattractant protein-1 expression and macrophage infiltration in gliomas. Acta Neuropathol. 1997; 93 (5): 518-27. https://doi.org/10.1007/s004010050647.
  21. Zhu X.J., Yang Z.F., Chen Y., Wang J., Rosmarin A.G. P.U.1 is essential for CD11c expression in CD8(+)/CD8(-) lymphoid and monocyte-derived dendritic cells during GM-CSF or FLT3L-induced differentiation. PLoS One. 2012; 7 (12): e52141. https://doi.org/10.1371/journal.pone.0052141.

补充文件

附件文件
动作
1. JATS XML
下载

版权所有 © Russkiy Vrach Publishing House, 2021