The effect of plerixafor on the migration of immune stem cells into the tumor site and survival of rats with C6 glioma (experimental study)
https://doi.org/10.56618/2071-2693_2024_16_3_104
EDN: HQPBGA
Abstract
INTRODUCTION. Glioblastoma (GB) is a lethal recurrent glial tumor.
AIM. To study the effect of the CXCR4 inhibitor plerixafor on the processes of homing of bone marrow stem cells (BMSCs) into the tumor site and to evaluate the survival of animals after chemoradiotherapy (CRT).
MATERIALS AND METHODS. C6 cells and Wistar rats were used. The experiment was approved by the local ethics committee. The methods used were cultural, flow cytometry, experimental surgery, CRT, morphological, immunohistochemical and enzyme-linked immunosorbent analysis, Kaplan – Meier survival assessment.
RESULTS. Administration of granulocyte colony-stimulating factor (G-CSF) to rats with C6 glioma increases the content of BMSCs in the bloodstream by 24.4 times, the combination of G-CSF and plerixafor (PLX) – by 32.9 times. Stimulation with G-CSF increases the content of proliferating cells in the tumor and enriches it with microglial markers, which is accompanied by an increase in the content of TGFβ1 82.4±11.4 ng/ml (versus 38.8±16.3 ng/ml in the control), wnt3A and wnt5A – 52.2±6.4 and 100±11.2 ng/ml (versus 18.6±9.4 and 38.6±14.2 ng/ml in control) and β-catenin – 174±11.2 ng/ml (versus 82.2±16.4 ng/ml in the control). This effect is absent in rats treated with G-CSF and PLF. The median survival of rats receiving CRT was 35 days: rats receiving CRT + G-CSF or PLX were 49 and 51 days, CRT + G-CSF + PLF was 64 days.
CONCLUSIONS. Plerixafor enhances the recruiting effect of G-CSF on BMSCs, disrupts the processes of their migration and homing into the neoplastic lesion, which is accompanied by a decrease in the number of proliferating elements and microglial cells, a decrease in the content of TGFβ1, wnt ligands and β-catenin in the brain substance and an increase in experimental survival animals with C6 glioma.
About the Authors
O. I. Pak
Far Eastern Federal University
Russian Federation
Russian Federation
Oleg I. Pak – Cand. of Sci. (Med.), Associate Professor at the School of Medicine and Lifescience
39 Okeansky Avenue, Vladivostok, 690090
A. A. Kosianova
Far Eastern Federal University
Russian Federation
Russian Federation
Aleksandra A. Kosianova – Cand. of Sci. (Biol.), Senior Lecturer at the Department of Farmacy and Farmacology, School of Medicine and Lifescience
39 Okeansky Avenue, Vladivostok, 690090
S. V. Zaitsev
Far Eastern Federal University
Russian Federation
Russian Federation
Sergei V. Zaitsev – Cand. of Sci. (Biol.), Head at the Laboratory of the Molecular and Cellular Neurobiology, Associate Professor at the Department of Farmacy and Farmacology, School of Medicine and Lifescience
39 Okeansky Avenue, Vladivostok, 690090
I. S. Bryukhovetskiy
Far Eastern Federal University
Russian Federation
Russian Federation
Igor S. Bryukhovetskiy – Dr. of Sci. (Med.), Associate Professor, Science Director at the Medical Complex, Professor at the Department of Farmacy and Farmacology, School of Medicine and Lifescience
39 Okeansky Avenue, Vladivostok, 690090
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Review
For citations:
Pak O.I., Kosianova A.A., Zaitsev S.V., Bryukhovetskiy I.S. The effect of plerixafor on the migration of immune stem cells into the tumor site and survival of rats with C6 glioma (experimental study). Russian Neurosurgical Journal named after Professor A. L. Polenov. 2024;16(3):104-113. (In Russ.) https://doi.org/10.56618/2071-2693_2024_16_3_104. EDN: HQPBGA
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