摘要
目的:目前的工作旨在评估 proBDNF/BDNF 在脑微血管内皮细胞与一直被报道会导致脑转移的 MDA-MB-231 乳腺癌细胞系之间相互作用中的作用。背景:乳腺癌脑转移(BM)是一个重要的健康问题,治疗选择有限。 BM 的发展是一个多步骤的过程,需要与脑血管系统和肿瘤血液供应的发展不断相互作用。基于在乳腺癌转移中拮抗血管内皮生长因子的抗血管生成方式的益处并未证明是有效的。脑源性神经营养因子 (BDNF) 是一种具有血管生成作用的神经营养因子。缺乏关于 BDNF 参与转移性乳腺癌与脑微血管内皮细胞 (HBEC-5i) 相互作用的数据。方法:使用自适应转移设计,研究了 HBEC-5i 和 MDAMB-231 细胞之间的串扰。 HBEC-5i 用 MDA-MB-231 条件培养基处理,并在迁移和体外管形成测定中使用基于释放和抑制剂的测定来评估 BDNF/proBDNF 在相互作用中的参与。结果:MDA-MB-231 和 HBEC-5i 释放总 BDNF(分别为 250 和 80 pg/ml)。 MDA-MB-231 条件培养基抑制 HBEC-5i 迁移超过 80% (p<0.05) 和管形成 75% (p<0.05)。中和成熟的 BDNF 不会改变 MDA-MB-231 诱导的抗血管生成作用,通过拮抗 proBDNF 完全减弱了这种作用。 MDA-MB-231 释放 proBDNF (131.5 pg/ml),释放的 BDNF 总量中超过 60% 处于前体形式。结论:proBDNF是乳腺癌诱导的脑内皮细胞抗血管生成作用的新介质。
关键词: BDNF、血管生成、脑、乳腺癌、内皮细胞、GSK-3β。
Current Molecular Medicine
Title:ProBDNF is a Novel Mediator of the Interaction Between MDA-MB- 231 Breast Cancer Cells and Brain Microvascular Endothelial Cells
Volume: 21 Issue: 10
关键词: BDNF、血管生成、脑、乳腺癌、内皮细胞、GSK-3β。
摘要:
Aim: The current work aims to assess the role of proBDNF/BDNF in the interaction between brain microvascular endothelial cells and the MDA-MB-231 breast cancer cell line that has been consistently reported to cause brain metastasis.
Background: Breast cancer brain metastasis (BM) is a significant health problem with limited therapeutic options. The development of BM is a multistep process that requires constant interaction with brain vasculature and the development of tumor blood supply. The benefits of anti-angiogenic modalities, based on antagonizing vascular endothelial growth factor in breast cancer metastasis, did not prove to be effective. Brain-derived neurotrophic factor (BDNF) is a neurotrophin with a reported angiogenic effect. There is a lack of data regarding the involvement of BDNF in metastatic breast cancer interaction with brain microvascular endothelial cells (HBEC-5i).
Methods: Using an adaptive transfer design, the cross-talk between HBEC-5i and MDAMB- 231 cell was investigated. HBEC-5i were treated with MDA-MB-231-conditioned media, and the involvement of BDNF/proBDNF in the interaction was assessed using both release and inhibitor-based assays in migration and in vitro tube formation assay.
Results: MDA-MB-231 and HBEC-5i released total BDNF (250 vs. 80 pg/ml, respectively). MDA-MB-231 conditioned media inhibited the migration of HBEC-5i by more than 80% (p<0.05) and tube formation by 75% (p<0.05). Neutralizing mature BDNF did not alter the MDA-MB-231 induced anti-angiogenic effect, which was completely blunted by antagonizing proBDNF. MDA-MB-231 released proBDNF (131.5 pg/ml), and more than 60% of total BDNF released was in the pro-form.
Conclusion: proBDNF is a novel mediator of breast cancer-induced anti-angiogenic effect in brain endothelial cells.
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Cite this article as:
ProBDNF is a Novel Mediator of the Interaction Between MDA-MB- 231 Breast Cancer Cells and Brain Microvascular Endothelial Cells, Current Molecular Medicine 2021; 21 (10) . https://dx.doi.org/10.2174/1566524020666201120142717
DOI https://dx.doi.org/10.2174/1566524020666201120142717 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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