Morphological and Immunophenotypic Characterization of Perivascular Interstitial Cells in Human Glioma: Telocytes, Pericytes, and Mixed Immunophenotypes

Overview

Journal Oncotarget

Specialty Oncology

Date 2020 Feb 18

PMID 32064038

Citations 4

Authors

Lubov Mitrofanova

Anton Hazratov

Boris Galkovsky

Andrey Gorshkov

Danila Bobkov

Dmitry Gulyaev

Evgeny Shlyakhto

Affiliations

Soon will be listed here.

Abstract

Objective: Morphological study of Tc and Pc roles in GBM.

Materials And Methods: Samples from 15 GBM, 10 diffuse astrocytoma, as well as 5 control samples were studied. We used immunohistochemistry (IHC) with antibodies (Abs) to GFAP, Ki-67, CD117, NeuroD1, NG2, CD34, and SMA. Confocal laser scanning microscopy (CLSM) of 4 glioma tissue cultures and 4 GBM sections was performed with GFAP, CD117, CD34/connexin43, NeuroD1/connexin43, CD34/NG2 and CD13/CD117 Abs. Electron microscopy (EM) of GBM was performed in 4 cases.

Results: The presence of Tcs and Pcs was shown in GBM (IHC, EM, CLSM) and glioma cultures (CLSM). The Tc immunophenotype was CD117/CD34/connexin43/NeuroD1. The Pc immunophenotype was SMA/NG2/CD13. The number of Tcs in GBM specimens was 10 times higher than in astrocytoma. We also identified CD13/CD117 and CD34/NG2 co-expressing cells in GBM blood vessels.

Conclusion: Four immunophenotypes were found in GBM vessels, corresponding to endotheliocytes, Pcs, Tcs, and a mixed Pc/Tc immunophenotype. These and forthcoming improvements in our understanding of the origin and function of Tcs, including their relationship with Pcs, are necessary steps in oncology. Study of these cell types (Tcs, Pcs) and their roles in brain tumor oncogenesis will likely enable improved targeted therapies and support development of new forms of anti-neoplastic drugs.

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References

Kostin S . Cardiac telocytes in normal and diseased hearts. Semin Cell Dev Biol. 2016; 55:22-30. DOI: 10.1016/j.semcdb.2016.02.023. View

Passlick S, Grauer M, Schafer C, Jabs R, Seifert G, Steinhauser C . Expression of the γ2-subunit distinguishes synaptic and extrasynaptic GABA(A) receptors in NG2 cells of the hippocampus. J Neurosci. 2013; 33(29):12030-40. PMC: 6794062. DOI: 10.1523/JNEUROSCI.5562-12.2013. View

Dore-Duffy P, Katychev A, Wang X, Van Buren E . CNS microvascular pericytes exhibit multipotential stem cell activity. J Cereb Blood Flow Metab. 2006; 26(5):613-24. DOI: 10.1038/sj.jcbfm.9600272. View

Mou Y, Wang Y, Li J, Lu S, Duan C, Du Z . Immunohistochemical characterization and functional identification of mammary gland telocytes in the self-assembly of reconstituted breast cancer tissue in vitro. J Cell Mol Med. 2012; 17(1):65-75. PMC: 3823137. DOI: 10.1111/j.1582-4934.2012.01646.x. View

Cretoiu S, Cretoiu D, Marin A, Radu B, Popescu L . Telocytes: ultrastructural, immunohistochemical and electrophysiological characteristics in human myometrium. Reproduction. 2013; 145(4):357-70. PMC: 3636525. DOI: 10.1530/REP-12-0369. View

Nakano M, Tamura Y, Yamato M, Kume S, Eguchi A, Takata K . NG2 glial cells regulate neuroimmunological responses to maintain neuronal function and survival. Sci Rep. 2017; 7:42041. PMC: 5307324. DOI: 10.1038/srep42041. View

Bei Y, Wang F, Yang C, Xiao J . Telocytes in regenerative medicine. J Cell Mol Med. 2015; 19(7):1441-54. PMC: 4511344. DOI: 10.1111/jcmm.12594. View

Ratajczak M, Ratajczak D, Pedziwiatr D . Extracellular Microvesicles (ExMVs) in Cell to Cell Communication: A Role of Telocytes. Adv Exp Med Biol. 2016; 913:41-49. DOI: 10.1007/978-981-10-1061-3_3. View

Winkler E, Bell R, Zlokovic B . Pericyte-specific expression of PDGF beta receptor in mouse models with normal and deficient PDGF beta receptor signaling. Mol Neurodegener. 2010; 5:32. PMC: 2936891. DOI: 10.1186/1750-1326-5-32. View

10.

Milia A, Ruffo M, Manetti M, Rosa I, Conte D, Fazi M . Telocytes in Crohn's disease. J Cell Mol Med. 2013; 17(12):1525-36. PMC: 3914651. DOI: 10.1111/jcmm.12177. View

11.

Zhao C, Deng W, Gage F . Mechanisms and functional implications of adult neurogenesis. Cell. 2008; 132(4):645-60. DOI: 10.1016/j.cell.2008.01.033. View

12.

Dore-Duffy P, Cleary K . Morphology and properties of pericytes. Methods Mol Biol. 2010; 686:49-68. DOI: 10.1007/978-1-60761-938-3_2. View

13.

Yue W, Chen Z . Does vasculogenic mimicry exist in astrocytoma?. J Histochem Cytochem. 2005; 53(8):997-1002. DOI: 10.1369/jhc.4A6521.2005. View

14.

Paul G, Ozen I, Christophersen N, Reinbothe T, Bengzon J, Visse E . The adult human brain harbors multipotent perivascular mesenchymal stem cells. PLoS One. 2012; 7(4):e35577. PMC: 3327668. DOI: 10.1371/journal.pone.0035577. View

15.

Popescu L, Ciontea S, Cretoiu D . Interstitial Cajal-like cells in human uterus and fallopian tube. Ann N Y Acad Sci. 2007; 1101:139-65. DOI: 10.1196/annals.1389.022. View

16.

Zheng Y, Cretoiu D, Yan G, Cretoiu S, Popescu L, Wang X . Comparative proteomic analysis of human lung telocytes with fibroblasts. J Cell Mol Med. 2014; 18(4):568-89. PMC: 4000110. DOI: 10.1111/jcmm.12290. View

17.

Oyama K, Sanno N, Teramoto A, Osamura R . Expression of neuro D1 in human normal pituitaries and pituitary adenomas. Mod Pathol. 2001; 14(9):892-9. DOI: 10.1038/modpathol.3880408. View

18.

Tilton R, Miller E, Kilo C, Williamson J . Pericyte form and distribution in rat retinal and uveal capillaries. Invest Ophthalmol Vis Sci. 1985; 26(1):68-73. View

19.

Armulik A, Genove G, Mae M, Nisancioglu M, Wallgard E, Niaudet C . Pericytes regulate the blood-brain barrier. Nature. 2010; 468(7323):557-61. DOI: 10.1038/nature09522. View

20.

Popescu L, Faussone-Pellegrini M . TELOCYTES - a case of serendipity: the winding way from Interstitial Cells of Cajal (ICC), via Interstitial Cajal-Like Cells (ICLC) to TELOCYTES. J Cell Mol Med. 2010; 14(4):729-40. PMC: 3823108. DOI: 10.1111/j.1582-4934.2010.01059.x. View