Morphological and immunophenotypic characterization of perivascular interstitial cells in human glioma: Telocytes, pericytes, and mixed immunophenotypes

Lubov Mitrofanova; Anton Hazratov; Boris Galkovsky; Andrey Gorshkov; Danila Bobkov; Dmitry Gulyaev; Evgeny Shlyakhto

doi:10.18632/oncotarget.27340

Morphological and immunophenotypic characterization of perivascular interstitial cells in human glioma: Telocytes, pericytes, and mixed immunophenotypes

Oncotarget. 2020 Jan 28;11(4):322-346. doi: 10.18632/oncotarget.27340.

Authors

Lubov Mitrofanova¹, Anton Hazratov¹, Boris Galkovsky¹, Andrey Gorshkov^{1

2}, Danila Bobkov^{2

3}, Dmitry Gulyaev⁴, Evgeny Shlyakhto⁵

Affiliations

¹ Almazov National Medical Research Centre, Pathomorphology Research Laboratory, St. Petersburg, Russia.
² Smorodintsev Research Institute of Influenza, Laboratory of Intracellular Signaling and Transport, St. Petersburg, Russia.
³ Institute of Cytology of the Russian Academy of Science, Laboratory of Cell Biology in Culture, St. Petersburg, Russia.
⁴ Almazov National Medical Research Centre, Research Department of Neurosurgery, St. Petersburg, Russia.
⁵ Almazov National Medical Research Centre, General Director, St. Petersburg, Russia.

Abstract

Telocytes (Tcs) and pericytes (Pcs) are two types of perivascular interstitial cell known to be widespread in various organs and tissues, including the brain. We postulated that Tcs and Pcs may be involved in glioblastoma (GBM) neovascularization.

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.

Keywords: confocal microscopy; glioblastoma; pericytes; primary culture of glioma telocytes; telocytes.