Immune microenvironment of experimental rat C6 gliomas resembles human glioblastomas

Gieryng, Anna; Pszczolkowska, Dominika; Bocian, Katarzyna; Dąbrowski, Michał; Rajan, Wenson D.; Kloss, Michal; Mieczkowski, Jakub; Kamińska, Bożena

doi:10.1038/s41598-017-17752-w

Cited by 76 publications

(80 citation statements)

References 85 publications

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“…Similarly, in human glioma samples obtained from patients, (Monif et al, 2014) observed P2X7 overexpression in the tumor when compared to the normal brain, especially in the glioma cells on the tumor periphery, but also in the microglia and, to a lower extent, in the astrocytes associated with the tumor. Concordantly, it is known from long time that activated microglia show increased activation of P2X7 receptor in various pathological states (Ferrari et al, 1999;Ferrari et al, 1997;Hide et al, 2002) and it is well established that it contributes to the glioma-supporting microenvironment (Gieryng et al, 2017).…”

Section: Introductionmentioning

confidence: 95%

P2X7 receptor activity landscape in rat and human glioma cell lines

2020

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P2X7 is a commonly expressed purinergic receptor, which functions as a cation-permeable channel in the plasma membrane. In certain circumstances, the receptor may also form a large transmembrane pore what results in cell death. P2X7 receptors control numerous physiological and pathological cellular processes and their overexpression is often associated with cancer progression. As nucleotides are important signaling molecules in the central nervous system, P2X7 plays also an important but ambiguous role in glioma biology with contrary observations originating from different glioma models. Therefore, the aim of our research was to investigate P2X7 receptor expression and functions in three human (U-87 MG, U-138 MG, U-251 MG) and one rat (C6) glioma cell lines. Although the receptor mRNA and protein were present in all the studied cells, we found profound differences in their level. We also encountered a problem with one human cell lines authenticity (U-87 MG) and excluded it from most of the experiments. Interestingly, there was no clear dependency between P2X7 receptor level, calcium signal and pore formation ability in the studied glioma lines. In U-138 human cell line, the receptor seemed to be inactive, while in U-251 human and C6 rat cell line its activation resulted in calcium influx and large pore formation. However, the viability of studied cells upon the administration of specific P2X7 agonist -BzATP -was not affected for U-138 and U-251, whereas for C6 cells a stimulatory effect was observed. Our results stress the variability of P2X7 signaling in glioma models and the need for future research which would take into account the complicated landscape of the receptor signaling in the brain.

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Section: Introductionmentioning

confidence: 95%

P2X7 receptor activity landscape in rat and human glioma cell lines

2020

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“…Several evidences indicate the pro-tumorigenic effect of microglia in gliomas (66,(119)(120)(121)(122)(123). In the present study, we identified microglia expressing TLR4 protein around vessels and hypoxic areas.…”

Section: Discussionsupporting

confidence: 64%

Receptor do tipo Toll 4 dentre os TLRs de membrana plasmática possui um papel na malignidade de astrocitomas

Moretti¹,

Marie²

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2018Agradecimentos "Há em cada um e nós, uma floresta virgem, emaranhada, inexplorada; um campo nevado onde não se veem nem pegadas de pássaros." Virginia Wolf No processo de construção dessa dissertação de mestrado me deparei com grandes dificuldades que com um grande esforço foram absorvidas e me permitiram que eu amadurecesse profissionalmente e pessoalmente. E para que isso ocorresse obtive a ajuda e o apoio da Profª Drª Suely Marie, que foi além de orientadora e com todo seu empenho e dedicação permitiu que eu pudesse realizar esse trabalho. E com grande ajuda da Dra. Sueli Oba-Shinjo que proporciona o funcionamento a todo vapor do laboratório LIM15 nos deixando realizar grandes feitos. Às duas meus mais sinceros agradecimentos. E às pessoas presentes em nossa rotina, que com muito humor fizeram meus dias mais animados e proveitosos. Agradeço às meninas do LIM-15 Stella Cavalcante, por toda ajuda, compreensão e companhia. À Daiane Franco, por toda ajuda no início do mestrado, participando e me ajudando na elaboração dos experimentos. À Paula Sola que com toda dedicação me ensinou a trabalhar com biologia molecular. À Roseli Silva e Laís Cavalca que me ensinaram e ajudaram no trabalho com cultura celular. À Fernanda Serachi, por toda descontração, e companhia nos almoços e lanches do McDonalds, à Talita Laurentino por toda ajuda, à Natália Cagnin por me tirar da rotina e me arrastar para alguns dias de sol, à Adaliana Moussessian, Marina Trombetta, Yollanda Moreira, Keyde Melo, Nathalia Villa, Tawany Carvalho, Amanda Narcizo, Camila Dantas, Mariana Molina. Muito obrigada à todas, sem vocês meus dias com certeza não seriam tão agradáveis. E aos funcionários, Eliene, Rosa, Nice, Luís, Márcia, Darcy e Camila. E a todos que colaboraram com o grupo LIM-15, que sempre acabam nos ajudando e muito na parte científica. Agradeço ao Prof. Bart Eggen, Profa. Ody Sibon, Nieske Brouwer, Dr. Antonio Lerario, à Dipika Mohan, ao confocal do CEFAP comandado pelo Mário Costa.Ao grupo de neurocirurgia do Hospital das Clínicas que se engajaram há mais de dez anos nesse projeto e possibilitaram a construção do biorrepositório que até hoje permite que façamos grandes projetos. E àquelas pessoas que ficam no plano de fundo que me apoiam emocionalmente. Sinto que sou uma pessoa extremamente privilegiada por possuir a família que tenho, e tudo que eu faço sei que tenho o apoio e a compreensão deles que não me deixaram cair. Aos meus pais e minha irmã agradeço por tudo, porque sem eles não seria nada. Agradeço também aos meus amigos, pessoas extraordinárias que me inspiram cada um à sua maneira e não me deixam parar. À Alessandra e ao Caio, acho que quase 20 anos na minha vida não consigo nem pensar em quem eu seria sem eles. Ao meu grupo querido que me xingam por eu não estar presente, mas eu sei que o que mais querem é minha felicidade, e eu agradeço por quererem me tirar de casa, me tirar da zona de conforto, Salsicha, Aline, Moreno, Fininho e Vandinha muito obrigada por tudo. E também à Alice, Gabriella, Coração, Yasmim, Chico, Pry...

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“…Additionally, numerous other preclinical studies have highlighted the tumor-promoting and immunosuppressive roles of these cells in GBM [2,[24][25]. However, unlike promising preclinical studies, efforts to deplete TAMCs in GBM patients have been disappointing.…”

Section: Discussionmentioning

confidence: 99%

Preclinical immunoPET imaging of glioblastoma-infiltrating myeloid cells using Zirconium-89-labeled anti-CD11b antibody

Nigam

McCarl

Kumar

et al. 2019

Preprint

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Purpose. Glioblastoma is a lethal brain tumor, heavily infiltrated by tumor-associated myeloid cells (TAMCs). TAMCs are emerging as a promising therapeutic target as they suppress antitumor immune responses and promote tumor cell growth. Quantifying TAMCs using non-invasive immunoPET could facilitate patient stratification for TAMC-targeted treatments and monitoring of treatment efficacy. As TAMCs uniformly express the cell surface marker, integrin CD11b, we evaluated a 89 Zr-labeled anti-CD11b antibody for non-invasive imaging of TAMCs in a syngeneic orthotopic mouse glioma model. Procedures.A human/mouse cross-reactive anti-CD11b antibody (clone M1/70) was conjugated to a DFO chelator and radiolabeled with Zr-89. PET/CT and biodistribution with or without a blocking dose of anti-CD11b Ab were performed 72 hours post-injection of 89 Zr-anti-CD11b Ab in mice bearing established orthotopic syngeneic GL261 gliomas. Flow cytometry and immunohistochemistry of dissected GL261 tumors were conducted to confirm the presence of CD11b + TAMCs.Results. Significant uptake of 89 Zr-anti-CD11b Ab was detected at the tumor site (SUVmean = 2.60 ± 0.24) compared with the contralateral hemisphere (SUVmean = 0.6 ± 0.11). Blocking with a 10-fold lower specific activity of 89 Zr-anti-CD11b Ab markedly reduced the SUV in the right brain (SUVmean = 0.11 ± 0.06), demonstrating specificity. Spleen and lymph nodes (myeloid cell rich organs) also showed high uptake of the tracer, and biodistribution analysis correlated with the imaging results. CD11b expression within the tumor was validated using flow cytometry and immunohistochemistry, which showed high CD11b expression primarily in the tumoral hemisphere compared to the contralateral hemisphere.3 Conclusion. These data establish that 89 Zr-anti-CD11b Ab immunoPET targets CD11b + cells (TAMCs) with high specificity in a mouse model of GBM, demonstrating the potential for noninvasive quantification of tumor infiltrating CD11b + immune cells during disease progression and immunotherapy in patients with GBM.

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Immune microenvironment of experimental rat C6 gliomas resembles human glioblastomas

Cited by 76 publications

References 85 publications

P2X7 receptor activity landscape in rat and human glioma cell lines

P2X7 receptor activity landscape in rat and human glioma cell lines

Receptor do tipo Toll 4 dentre os TLRs de membrana plasmática possui um papel na malignidade de astrocitomas

Preclinical immunoPET imaging of glioblastoma-infiltrating myeloid cells using Zirconium-89-labeled anti-CD11b antibody

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