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胶质母细胞瘤细胞表达可被日常使用的药物激活的功能性细胞膜受体。

Glioblastoma cells express functional cell membrane receptors activated by daily used medical drugs.

作者信息

Kuhn Susanne A, Mueller Ulrike, Hanisch Uwe-K, Regenbrecht Christian R A, Schoenwald Ilona, Brodhun Michael, Kosmehl Hartwig, Ewald Christian, Kalff Rolf, Reichart Rupert

机构信息

Department of Neurosurgery, Medical Center, Friedrich-Schiller-University, Erlanger Allee 101, 07747 Jena, Germany.

出版信息

J Cancer Res Clin Oncol. 2009 Dec;135(12):1729-45. doi: 10.1007/s00432-009-0620-6. Epub 2009 Jun 19.

DOI:10.1007/s00432-009-0620-6
PMID:19543745
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2847174/
Abstract

PURPOSE

Calcium ions are highly versatile spacial and temporal intracellular signals of non-excitable cells and have an important impact on nearly every aspect of cellular life controlling cell growth, metabolism, fluid secretion, information processing, transcription, apoptosis, and motility. Neurons and glia respond to stimuli, including neurotransmitters, neuromodulators, and hormones, which increase the intracellular calcium concentration. The function of intracellular calcium in gliomas is unknown. Lots of daily used drugs may act via receptors that can be linked to the intracellular calcium system and therefore could influence glioma biology.

METHODS

Glioma cells were loaded with the calcium ion sensitive dye Fura 2-AM. Subsequently, cells were stimulated with 25 different medical drugs for 30 s. The increase of free intracellular calcium ions was measured and calculated by a microscope-camera-computer-unit.

RESULTS

Except for the buffer solution HEPES that served as negative control and for the cortisol derivative dexamethasone, all other 24 tested drugs induced a rise of intracellular calcium ions. The cellular calcium responses were classified into seven functional groups. The tested substances activated several types of calcium channels and receptors.

CONCLUSIONS

Our study impressively demonstrates that medical drugs are potent inducers of intracellular calcium signals. Totally unexpected, the results show a high amount of functional cellular receptors and channels on glioma cells, which could be responsible for certain biological effects like migration and cell growth. This calcium imaging study proves the usability of the calcium imaging as a screening system for functional receptors on human glioma cells.

摘要

目的

钙离子是非兴奋性细胞中高度通用的时空细胞内信号，对细胞生命的几乎每个方面都有重要影响，控制着细胞生长、代谢、液体分泌、信息处理、转录、凋亡和运动。神经元和神经胶质细胞对包括神经递质、神经调质和激素在内的刺激作出反应，这些刺激会增加细胞内钙浓度。胶质瘤中细胞内钙的功能尚不清楚。许多日常使用的药物可能通过与细胞内钙系统相关的受体起作用，因此可能影响胶质瘤生物学。

方法

用钙离子敏感染料Fura 2-AM加载胶质瘤细胞。随后，用25种不同的药物刺激细胞30秒。通过显微镜-相机-计算机单元测量并计算细胞内游离钙离子的增加。

结果

除用作阴性对照的缓冲溶液HEPES和皮质醇衍生物地塞米松外，所有其他24种测试药物均诱导细胞内钙离子升高。细胞钙反应分为七个功能组。测试物质激活了几种类型的钙通道和受体。

结论

我们的研究令人印象深刻地表明，药物是细胞内钙信号的有效诱导剂。结果完全出乎意料，显示胶质瘤细胞上有大量功能性细胞受体和通道，这可能是迁移和细胞生长等某些生物学效应的原因。这项钙成像研究证明了钙成像作为人胶质瘤细胞功能性受体筛选系统的可用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/a0d1f1be5c21/432_2009_620_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/e9720daa6607/432_2009_620_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/f6ba53f58ba2/432_2009_620_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/61d59b11ff89/432_2009_620_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/b64ecc3af619/432_2009_620_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/3f0e53cac6d8/432_2009_620_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/e5590214c71c/432_2009_620_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/74e79aad8cab/432_2009_620_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/0705368f23e6/432_2009_620_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/a0d1f1be5c21/432_2009_620_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/e9720daa6607/432_2009_620_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/f6ba53f58ba2/432_2009_620_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/61d59b11ff89/432_2009_620_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/b64ecc3af619/432_2009_620_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/3f0e53cac6d8/432_2009_620_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/e5590214c71c/432_2009_620_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/74e79aad8cab/432_2009_620_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/0705368f23e6/432_2009_620_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/927b/11844791/a0d1f1be5c21/432_2009_620_Fig9_HTML.jpg

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