The Dynamics of Tumor-Infiltrating Myeloid Cell Activation and the Cytokine Expression Profile in a Glioma Resection Site during the Post-Surgical Period in Mice.
The Dynamics of Tumor-Infiltrating Myeloid Cell Activation and the Cytokine Expression Profile in a Glioma Resection Site during the Post-Surgical Period in Mice.
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DOI：
10.3390/brainsci12070893
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发表时间：
2022-07-07
期刊：
影响因子：
3.3
通讯作者：
Kucheryavykh, Lilia
中科院分区：
文献类型：
--
作者：
Ortiz-Rivera, Jescelica;Albors, Alejandro;Kucheryavykh, Yuriy;Harrison, Jeffrey K.;Kucheryavykh, Lilia
胶质母细胞瘤是最具侵袭性的脑癌，并且高度浸润有支持肿瘤生长和侵袭的髓系细胞（TIM）。肿瘤切除术是胶质母细胞瘤的主要治疗方法;然而，对肿瘤切除部位TIM的激活状态及其对胶质瘤再生长的影响知之甚少。利用C57 BL/6/GL 261小鼠胶质瘤种植模型，我们研究了手术后肿瘤切除区域的TIM状态。在肿瘤切除后0、1、4、7、14和21天分析从切除部位的脑组织分离的TIM。在手术切除后的前7天内检测到CD 86表达的增加，然后在切除后的第14天至第21天检测到CD 86表达的上调。与qRT-PCR相结合的细胞因子表达分析显示，与原发性植入肿瘤相比，从再生长肿瘤纯化的TIM中IL 4、IL 5、IL 10、IL 12、IL 17、血管内皮生长因子（VEGF）和单核细胞趋化蛋白1（MCP 1/CCL 2）持续上调。流式细胞术分析显示，与原发性植入肿瘤相比，再生长肿瘤中的CD 86 +/CD 206+群体增加。总的来说，我们发现原发性植入肿瘤和切除后再生长肿瘤中的TIM表现出不同的表型和细胞因子表达模式。
Glioblastoma is the most aggressive brain cancer and is highly infiltrated with cells of myeloid lineage (TIM) that support tumor growth and invasion. Tumor resection is the primary treatment for glioblastoma; however, the activation state of TIM at the site of tumor resection and its impact on glioma regrowth are poorly understood. Using the C57BL/6/GL261 mouse glioma implantation model, we investigated the state of TIM in the tumor resection area during the post-surgical period. TIM isolated from brain tissue at the resection site were analyzed at 0, 1, 4, 7, 14, and 21 days after tumor resection. An increase in expression of CD86 during the first 7 days after surgical resection and then upregulation of arginase 1 from the 14th to 21st days after resection were detected. Cytokine expression analysis combined with qRT-PCR revealed sustained upregulation of IL4, IL5, IL10, IL12, IL17, vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein 1 (MCP1/CCL2) in TIM purified from regrown tumors compared with primary implanted tumors. Flow cytometry analysis revealed increased CD86+/CD206+ population in regrown tumors compared with primary implanted tumors. Overall, we found that TIM in primary implanted tumors and tumors regrown after resection exhibited different phenotypes and cytokine expression patterns.
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