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Article

Crosstalk between β-Catenin and CCL2 Drives Migration of Monocytes towards Glioblastoma Cells

1
Department of Neurosurgery, University Hospital Düsseldorf, 40225 Dusseldorf, Germany
2
Department of Pathology, University of Otago, Dunedin 9016, New Zealand
3
Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Düsseldorf, 40225 Dusseldorf, Germany
4
State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China
5
Genome and Computational Biology Lab, Department of Biotechnology, Mohanlal Sukhadia University, Udaipur 313001, India
6
Department of Stereotactic and Functional Neurosurgery, University Hospital Bonn, 53127 Bonn, Germany
7
Northumbria Healthcare NHS Foundation Trust, Newcastle upon Tyne NE27 0QJ, UK
8
Department of Surgical Sciences, University of Otago, Dunedin 9016, New Zealand
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(9), 4562; https://doi.org/10.3390/ijms23094562
Submission received: 14 March 2022 / Revised: 13 April 2022 / Accepted: 14 April 2022 / Published: 20 April 2022

Abstract

Isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) is a fast growing and highly heterogeneous tumor, often characterized by the presence of glioblastoma stem cells (GSCs). The plasticity of GSCs results in therapy resistance and impairs anti-tumor immune response by influencing immune cells in the tumor microenvironment (TME). Previously, β-catenin was associated with stemness in GBM as well as with immune escape mechanisms. Here, we investigated the effect of β-catenin on attracting monocytes towards GBM cells. In addition, we evaluated whether CCL2 is involved in β-catenin crosstalk between monocytes and tumor cells. Our analysis revealed that shRNA targeting β-catenin in GBMs reduces monocytes attraction and impacts CCL2 secretion. The addition of recombinant CCL2 restores peripheral blood mononuclear cells (PBMC) migration towards medium (TCM) conditioned by shβ-catenin GBM cells. CCL2 knockdown in GBM cells shows similar effects and reduces monocyte migration to a similar extent as β-catenin knockdown. When investigating the effect of CCL2 on β-catenin activity, we found that CCL2 modulates components of the Wnt/β-catenin pathway and alters the clonogenicity of GBM cells. In addition, the pharmacological β-catenin inhibitor MSAB reduces active β-catenin, downregulates the expression of associated genes and alters CCL2 secretion. Taken together, we showed that β-catenin plays an important role in attracting monocytes towards GBM cells in vitro. We hypothesize that the interactions between β-catenin and CCL2 contribute to maintenance of GSCs via modulating immune cell interaction and promoting GBM growth and recurrence.
Keywords: glioblastoma; GSCs; β-catenin; Wnt; CCL2; monocytes; immune evasion; MSAB glioblastoma; GSCs; β-catenin; Wnt; CCL2; monocytes; immune evasion; MSAB

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MDPI and ACS Style

Aretz, P.; Maciaczyk, D.; Yusuf, S.; Sorg, R.V.; Hänggi, D.; Liu, H.; Liu, H.; Dakal, T.C.; Sharma, A.; Bethanabatla, R.; et al. Crosstalk between β-Catenin and CCL2 Drives Migration of Monocytes towards Glioblastoma Cells. Int. J. Mol. Sci. 2022, 23, 4562. https://doi.org/10.3390/ijms23094562

AMA Style

Aretz P, Maciaczyk D, Yusuf S, Sorg RV, Hänggi D, Liu H, Liu H, Dakal TC, Sharma A, Bethanabatla R, et al. Crosstalk between β-Catenin and CCL2 Drives Migration of Monocytes towards Glioblastoma Cells. International Journal of Molecular Sciences. 2022; 23(9):4562. https://doi.org/10.3390/ijms23094562

Chicago/Turabian Style

Aretz, Philippe, Donata Maciaczyk, Suad Yusuf, Rüdiger V. Sorg, Daniel Hänggi, Hongjia Liu, Hongde Liu, Tikam Chand Dakal, Amit Sharma, Ramakrishna Bethanabatla, and et al. 2022. "Crosstalk between β-Catenin and CCL2 Drives Migration of Monocytes towards Glioblastoma Cells" International Journal of Molecular Sciences 23, no. 9: 4562. https://doi.org/10.3390/ijms23094562

APA Style

Aretz, P., Maciaczyk, D., Yusuf, S., Sorg, R. V., Hänggi, D., Liu, H., Liu, H., Dakal, T. C., Sharma, A., Bethanabatla, R., Neumann, S., & Maciaczyk, J. (2022). Crosstalk between β-Catenin and CCL2 Drives Migration of Monocytes towards Glioblastoma Cells. International Journal of Molecular Sciences, 23(9), 4562. https://doi.org/10.3390/ijms23094562

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