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Differential Ca2+ responses and store operated Ca2+ entry in primary cells from human brain tumors
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 5.1 ) Pub Date : 2021-05-14 , DOI: 10.1016/j.bbamcr.2021.119060
Elena Hernando-Pérez 1 , Enrique Pérez-Riesgo 1 , Santiago Cepeda 2 , Ignacio Arrese 2 , Rosario Sarabia 2 , Carlos Villalobos 1 , Lucía Núñez 3
Affiliation  

Brain tumors comprise a large series of tumor cancer from benign to highly malignant gliomas and metastases from primary tumors outside the brain. Intracellular Ca2+ homeostasis is involved in a large series of cell functions including cell proliferation, migration, and cell death. Store-operated Ca2+ entry (SOCE), the most important Ca2+ entry pathway in non-excitable cells, is involved in cell proliferation and migration and enhanced in tumor cells from breast cancer, colon cancer and cell lines derived from glioblastoma but there are almost no studies in human primary glioblastoma cells or other brain tumors. We have developed a single procedure to obtain primary cells from a large series (n = 49) of human brain tumors including schwannomas, meningiomas, oligodendrogliomas, astrocytomas, glioblastomas and brain metastases from ovary, breast and lung. Cells were characterized by immunofluorescence and subjected to Ca2+ imaging to investigate resting intracellular Ca2+ levels, Ca2+ responses to physiological agonists as well as voltage-operated Ca2+ entry and SOCE. We found significant differences in resting intracellular Ca2+ and Ca2+ responses to plasma membrane depolarization and ATP among the different tumor cells. Only malignant tumor cells, displayed Ca2+ responses to ATP. SOCE is significantly increased in malignant gliomas whereas voltage-gated Ca2+ entry is decreased. In addition, SOCE is significantly larger in high grade gliomas than in low grade gliomas suggesting that SOCE increases with glioma progression. These data may provide new insights on the role of intracellular Ca2+ and purinergic signalling in brain tumors.



中文翻译:

来自人脑肿瘤的原代细胞中的差异 Ca2+ 反应和储存操作的 Ca2+ 进入

脑肿瘤包括从良性到高度恶性的神经胶质瘤以及来自脑外原发肿瘤的转移的一系列肿瘤癌症。细胞内 Ca 2+稳态涉及一系列细胞功能,包括细胞增殖、迁移和细胞死亡。Store-operated Ca 2+ entry (SOCE)是非兴奋性细胞中最重要的 Ca 2+进入途径,参与细胞增殖和迁移,并在乳腺癌、结肠癌和胶质母细胞瘤来源的细胞系中增强,但几乎没有关于人类原发性胶质母细胞瘤细胞或其他脑肿瘤的研究。我们开发了一个单一的程序来从大系列 ( n = 49) 人脑肿瘤,包括神经鞘瘤、脑膜瘤、少突胶质细胞瘤、星形细胞瘤、胶质母细胞瘤和来自卵巢、乳腺和肺的脑转移瘤。细胞通过免疫荧光表征并进行 Ca 2+成像以研究静息细胞内 Ca 2+水平、Ca 2+对生理激动剂的反应以及电压控制的 Ca 2+进入和 SOCE。我们发现不同肿瘤细胞之间静息细胞内 Ca 2+和 Ca 2+对质膜去极化和 ATP 的反应存在显着差异。只有恶性肿瘤细胞,显示 Ca 2+对 ATP 的反应。SOCE 在恶性胶质瘤中显着增加,而电压门控 Ca 2+进入减少。此外,高级别胶质瘤的 SOCE 明显大于低级别胶质瘤,这表明 SOCE 随胶质瘤进展而增加。这些数据可能为细胞内 Ca 2+和嘌呤能信号在脑肿瘤中的作用提供新的见解。

更新日期:2021-05-22
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