Glycocalyx transduces membrane leak in brain tumor cells exposed to sharp magnetic pulsing.
Glycocalyx transduces membrane leak in brain tumor cells exposed to sharp magnetic pulsing.
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DOI：
10.1016/j.bpj.2023.10.020
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发表时间：
2023-11
影响因子：
3.4
通讯作者：
Scott C. Johns;Purva Gupta;Yi-Hung Lee;J. Friend;M. Fuster
中科院分区：
文献类型：
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作者：
Scott C. Johns;Purva Gupta;Yi-Hung Lee;J. Friend;M. Fuster
电（E）或磁（B）场可能被利用来影响肿瘤细胞行为的机制仍然不清楚，这对翻译构成了障碍。我们在早期的研究中假设肺癌细胞的糖萼可能在介导由低能螺线管平台上产生的低频脉冲磁场（Lf-PMF）引起的质膜泄漏中起作用。在测试胶质母细胞瘤和神经母细胞瘤细胞时，已知这些细胞过度表达富含阴离子聚糖唾液酸（Sia）修饰的糖蛋白，将相同平台上的脑肿瘤细胞暴露于包括5分钟50 Hz Lf-PMF的脉冲串（dB/dt ≤ 2 T/s，10 ms脉冲宽度）诱导的蛋白酶泄漏非常温和，但显著高于对照未暴露细胞（暴露5分钟后，长期肿瘤细胞活力适度但显着降低）。使用明显更高的dB/dt系统（80 T/s脉冲，距离MagVenture线圈源5.9 cm处的脉冲宽度为70μs）诱导相同细胞的明显更大的泄漏，并且通过在暴露前立即用AUS唾液酸酶处理细胞来消除Sia完全消除了SH-SY 5 Y神经母细胞瘤细胞中的作用，部分消除了T98 G胶质母细胞瘤细胞中的作用。该系统表现出显著的泄漏（包括碘化丙啶的向内泄漏），在各种肿瘤细胞中在较低dB/dt下泄漏减少。通过在SH-SY 5 Y脑肿瘤细胞中用唾液酸酶预处理或在A549肺肿瘤细胞中用肝素裂解酶预处理消除Lf-PMF蛋白酶泄漏的能力表明重Sia或硫酸乙酰肝素糖胺聚糖糖萼修饰作为介导相应肿瘤细胞中Lf-PMF膜泄漏的主要聚糖种类的重要性。这种“第一物理”Lf-PMF肿瘤糖萼事件，与下游细胞应激，可能代表了一个关键的和“可调”的转导机制，取决于特征性阴离子聚糖过表达的不同的恶性肿瘤。
Mechanisms by which electric (E) or magnetic (B) fields might be harnessed to affect tumor cell behavior remain poorly defined, presenting a barrier to translation. We hypothesized in early studies that the glycocalyx of lung cancer cells might play a role in mediating plasma membrane leak by low-frequency pulsed magnetic fields (Lf-PMF) generated on a low-energy solenoid platform. In testing glioblastoma and neuroblastoma cells known to overexpress glycoproteins rich in modifications by the anionic glycan sialic acid (Sia), exposure of brain tumor cells on the same platform to a pulse train that included a 5 min 50Hz Lf-PMF (dB/dt ∼ 2 T/s at 10 ms pulse widths) induced a very modest but significant protease leak above that of control nonexposed cells (with modest but significant reductions in long-term tumor cell viability after the 5 min exposure). Using a markedly higher dB/dt system (80 T/s pulses, 70μs pulse-width at 5.9 cm from a MagVenture coil source) induced markedly greater leak by the same cells, and eliminating Sia by treating cells with AUS sialidase immediately preexposure abrogated the effect entirely in SH-SY5Y neuroblastoma cells, and partially in T98G glioblastoma cells. The system demonstrated significant leak (including inward leak of propidium iodide), with reduced leak at lower dB/dt in a variety of tumor cells. The ability to abrogate Lf-PMF protease leak by pretreatment with sialidase in SH-SY5Y brain tumor cells or with heparin lyase in A549 lung tumor cells indicated the importance of heavy Sia or heparan sulfate glycosaminoglycan glycocalyx modifications as dominant glycan species mediating Lf-PMF membrane leak in respective tumor cells. This "first-physical" Lf-PMF tumor glycocalyx event, with downstream cell stress, may represent a critical and "tunable" transduction mechanism that depends on characteristic anionic glycans overexpressed by distinct malignant tumors.