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Article

A Heterotypic Tridimensional Model to Study the Interaction of Macrophages and Glioblastoma In Vitro

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Instituto de Nanosistemas, Universidad Nacional de San Martín, 25 de Mayo 1021, San Martín, Buenos Aires 1650, Argentina
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Instituto de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Piso 9, Buenos Aires 1121, Argentina
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Instituto de Medicina Experimental (IMEX), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, Buenos Aires 1425, Argentina
*
Authors to whom correspondence should be addressed.
Academic Editor: Guillermo Gomez
Int. J. Mol. Sci. 2021, 22(10), 5105; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105105
Received: 26 March 2021 / Revised: 13 April 2021 / Accepted: 14 April 2021 / Published: 12 May 2021
Background: Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor, and macrophages account for 30–40% of its composition. Most of these macrophages derive from bone marrow monocytes playing a crucial role in tumor progression. Unraveling the mechanisms of macrophages-GBM crosstalk in an appropriate model will contribute to the development of specific and more successful therapies. We investigated the interaction of U87MG human GBM cells with primary human CD14+ monocytes or the THP-1 cell line with the aim of establishing a physiologically relevant heterotypic culture model. Methods: primary monocytes and THP-1 cells were cultured in the presence of U87MG conditioned media or co-cultured together with previously formed GBM spheroids. Monocyte differentiation was determined by flow cytometry. Results: primary monocytes differentiate to M2 macrophages when incubated with U87MG conditioned media in 2-dimensional culture, as determined by the increased percentage of CD14+CD206+ and CD64+CD206+ populations in CD11b+ cells. Moreover, the mitochondrial protein p32/gC1qR is expressed in monocytes exposed to U87MG conditioned media. When primary CD14+ monocytes or THP-1 cells are added to previously formed GBM spheroids, both invade and establish within them. However, only primary monocytes differentiate and acquire a clear M2 phenotype characterized by the upregulation of CD206, CD163, and MERTK surface markers on the CD11b+CD14+ population and induce alterations in the sphericity of the cell cultures. Conclusion: our results present a new physiologically relevant model to study GBM/macrophage interactions in a human setting and suggest that both soluble GBM factors, as well as cell-contact dependent signals, are strong inducers of anti-inflammatory macrophages within the tumor niche. View Full-Text
Keywords: glioblastoma multiforme; monocytes; macrophage polarization; 3D cultures; tumor-stromal interactions; CD206 glioblastoma multiforme; monocytes; macrophage polarization; 3D cultures; tumor-stromal interactions; CD206
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MDPI and ACS Style

Gattas, M.J.; Estecho, I.G.; Lago Huvelle, M.A.; Errasti, A.E.; Carrera Silva, E.A.; Simian, M. A Heterotypic Tridimensional Model to Study the Interaction of Macrophages and Glioblastoma In Vitro. Int. J. Mol. Sci. 2021, 22, 5105. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105105

AMA Style

Gattas MJ, Estecho IG, Lago Huvelle MA, Errasti AE, Carrera Silva EA, Simian M. A Heterotypic Tridimensional Model to Study the Interaction of Macrophages and Glioblastoma In Vitro. International Journal of Molecular Sciences. 2021; 22(10):5105. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105105

Chicago/Turabian Style

Gattas, María J., Ivana G. Estecho, María A. Lago Huvelle, Andrea E. Errasti, Eugenio A. Carrera Silva, and Marina Simian. 2021. "A Heterotypic Tridimensional Model to Study the Interaction of Macrophages and Glioblastoma In Vitro" International Journal of Molecular Sciences 22, no. 10: 5105. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105105

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