Antiangiogenic effects of melatonin in endothelial cell cultures
Antiangiogenic effects of melatonin in endothelial cell cultures
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DOI：
10.1016/j.mvr.2013.02.008
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发表时间：
2013-05-01
影响因子：
3.1
通讯作者：
Cos, Samuel
中科院分区：
文献类型：
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作者：
Alvarez-Garcia, Virginia;Gonzalez, Alicia;Cos, Samuel
内皮细胞是肿瘤微环境中的关键细胞元件之一，通过控制血管生成在癌症的生长和进展中发挥着至关重要的作用。肿瘤细胞产生的血管内皮生长因子（VEGF）对于乳腺癌的扩张至关重要，并且可能以旁分泌和自分泌方式发挥作用，促进内皮细胞的增殖、生长、存活和迁移。由于褪黑素通过减少恶性上皮细胞分泌VEGF来调节肿瘤微环境，并且还调节人乳腺癌细胞中的VEGF表达，因此本研究的目的是研究褪黑素对乳腺癌细胞促血管生成作用的抗血管生成活性。在这项工作中，我们证明褪黑素强烈抑制人脐静脉内皮细胞（HUVEC）的增殖以及侵袭/迁移。褪黑激素破坏管形成并抵消 VEGF 刺激的 HUVEC 管网络形成。此外，从人乳腺癌细胞收集的条件培养基具有血管生成活性并刺激小管长度形成，并且添加抗VEGF或褪黑激素可以显着抵消这种作用。褪黑激素还破坏预先形成的毛细血管网络。所有这些发现表明，褪黑激素可能在恶性上皮细胞和近端内皮细胞之间发生的旁分泌相互作用中发挥作用。褪黑素通过下调 VEGF 的作用，在减少内皮细胞增殖、侵袭、迁移和管形成方面发挥重要作用。总而言之，我们的研究结果表明，褪黑激素可能作为乳腺癌的抗血管生成剂有益，并可能在未来的临床应用中发挥作用。 (C) 2013 Elsevier Inc. 保留所有权利。
Endothelial cells represent one of the critical cellular elements in tumor microenvironment playing a crucial role in the growth and progression of cancer through controlling angiogenesis. Vascular endothelial growth factor (VEGF) produced from tumor cells is essential for the expansion of breast cancer and may function in both paracrine and autocrine manners to promote proliferation, growth, survival and migration of endothelial cells. Since melatonin regulates tumor microenvironment by decreasing the secretion of VEGF by malignant epithelial cells and also regulates VEGF expression in human breast cancer cells, the aim of the present study was to investigate the anti-angiogenic activity of melatonin against the pro-angiogenic effects of breast cancer cells.In this work, we demonstrate that melatonin strongly inhibited the proliferation as well as invasion/migration of human umbilical vein endothelial cells (HUVECs). Melatonin disrupted tube formation and counteracted the VEGF-stimulated tubular network formation by HUVEC. In addition, conditioned media collected from human breast cancer cells were angiogenically active and stimulated tubule length formation and this effect was significantly counteracted by the addition of anti-VEGF or melatonin. Melatonin also disintegrated preformed capillary network.All these findings demonstrate that melatonin may play a role in the paracrine interactions that take place between malignant epithelial cells and proximal endothelial cells. Melatonin could be important in reducing endothelial cell proliferation, invasion, migration and tube formation, through a downregulatory action on VEGF. Taken together, our findings suggest that melatonin could potentially be beneficial as an antiangiogenic agent in breast cancer with possible future clinical applications. (C) 2013 Elsevier Inc. All rights reserved.