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缺氧和常氧肿瘤分泌对脑内皮细胞(bEnd.3)增殖的旁分泌作用。

The Paracrine Effect of Hypoxic and Normoxic Cancer Secretion on the Proliferation of Brain Endothelial Cells (bEnd.3).

机构信息

Medical Bioscience Department, Faculty of Natural Sciences, University of the Western Cape, Robert Sobukwe Road, Bellville 7335, South Africa.

出版信息

Cells. 2022 Apr 2;11(7):1197. doi: 10.3390/cells11071197.

DOI:10.3390/cells11071197
PMID:35406760
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8997846/
Abstract

BACKGROUND

This study aimed to investigate the disruption of cell cycle phases of bEnd.3 cells exposed to cancer paracrine secretion. Cancer cells have been reported to use the secretion of paracrine factors to compromise the endothelial barrier to prepare for their passage into the parenchyma. As cancer cells are known to act differently under conditions of hypoxia, we investigated how conditional media (CM) derived from breast and glioblastoma cells incubated under conditions of normoxia and hypoxia would affect proliferation of brain endothelial cells (bEnd.3).

METHODS

Brain endothelial cells (bEnd.3) were cultivated with normoxic and hypoxic CM generated from breast cancer MCF7 cells and glioblastoma U-87 cells. Cell proliferation was evaluated using the trypan blue exclusion assay and phases of the cell cycle were evaluated using flow cytometry.

RESULTS

bEnd.3 proliferations was suppressed more aggressively with hypoxic CM after 72 and 96 h; cell cycle analysis showed that paracrine treatment tended to prevent BECs from entering the G2 phase, thus suppressing cell division.

CONCLUSIONS

MCF7 and U-87 cells induce suppressed proliferation of BECs deferentially under hypoxia by blocking cell cycle progression to the G2 phase.

摘要

背景

本研究旨在探究暴露于癌症旁分泌环境中的 bEnd.3 细胞的细胞周期各时相的改变。据报道,癌细胞利用旁分泌因子的分泌作用来破坏内皮屏障,为其向实质内转移做好准备。由于已知缺氧条件下癌细胞的行为有所不同,我们研究了在常氧和缺氧条件下孵育的乳腺癌 MCF7 细胞和脑胶质瘤 U-87 细胞产生的条件培养基(CM)如何影响脑内皮细胞(bEnd.3)的增殖。

方法

用常氧和缺氧条件下产生的乳腺癌 MCF7 细胞和脑胶质瘤 U-87 细胞的 CM 培养脑内皮细胞(bEnd.3)。用台盼蓝排斥试验评估细胞增殖,用流式细胞术评估细胞周期各时相。

结果

bEnd.3 在 72 和 96 小时后用缺氧 CM 增殖受到更强烈的抑制;细胞周期分析表明,旁分泌处理倾向于阻止 BEC 进入 G2 期,从而抑制细胞分裂。

结论

MCF7 和 U-87 细胞通过阻止细胞周期进入 G2 期,使 BEC 增殖受到不同程度的抑制,从而在缺氧条件下诱导 BEC 增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fef/8997846/037d8d57bf0f/cells-11-01197-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fef/8997846/163479e4f823/cells-11-01197-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fef/8997846/3ef91ae17517/cells-11-01197-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fef/8997846/d4f7d8669eca/cells-11-01197-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fef/8997846/037d8d57bf0f/cells-11-01197-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fef/8997846/163479e4f823/cells-11-01197-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fef/8997846/3ef91ae17517/cells-11-01197-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fef/8997846/d4f7d8669eca/cells-11-01197-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fef/8997846/037d8d57bf0f/cells-11-01197-g004.jpg

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本文引用的文献

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2
Differential Effects of Normoxic versus Hypoxic Derived Breast Cancer Paracrine Factors on Brain Endothelial Cells.常氧与低氧来源的乳腺癌旁分泌因子对脑内皮细胞的不同影响。
Biology (Basel). 2021 Nov 27;10(12):1238. doi: 10.3390/biology10121238.
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A vascularized tumoroid model for human glioblastoma angiogenesis.
用于人类胶质母细胞瘤血管生成的血管化肿瘤模型。
Sci Rep. 2021 Oct 1;11(1):19550. doi: 10.1038/s41598-021-98911-y.
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Tumor vessel co-option probed by single-cell analysis.单细胞分析探究肿瘤血管选择。
Cell Rep. 2021 Jun 15;35(11):109253. doi: 10.1016/j.celrep.2021.109253.
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Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia.缺氧对微血管内皮细胞代谢途径的影响。
PLoS One. 2020 Jul 9;15(7):e0232072. doi: 10.1371/journal.pone.0232072. eCollection 2020.
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Vessel co-option in glioblastoma: emerging insights and opportunities.血管生成拟态在胶质母细胞瘤中的作用:新的认识和机遇。
Angiogenesis. 2020 Feb;23(1):9-16. doi: 10.1007/s10456-019-09691-z. Epub 2019 Nov 2.
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Brain malignancies: Glioblastoma and brain metastases.脑恶性肿瘤:胶质母细胞瘤和脑转移瘤。
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