Scalia Alessandro, Doumani Lesly, Kindt Nadège, Journé Fabrice, Trelcat Anne, Carlier Stéphane
Department of Cardiology, Research Institute for Health Sciences and Technology, University of Mons (UMONS), 7000 Mons, Belgium.
Department of Clinical and Experimental Oncology, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, Belgium.
Biology (Basel). 2023 Jun 22;12(7):896. doi: 10.3390/biology12070896.
Cardiovascular diseases are the leading causes of death worldwide, closely followed by cancer. To investigate the impact of breast cancer cell lines (SKBR3, MCF-7, and MDA-MB-231) on endothelial cell adhesion, a blended medium containing 30% breast-cancer-conditioned medium was prepared. This medium was then exposed to human umbilical vein endothelial cells (HUVECs) and monocytes (THP-1) for 48 h. Homemade oxidized low-density lipoproteins (oxLDL) were optionally added to the blended medium. Immunofluorescence was performed to assess the expression of E-selectin, connexin-43, and ICAM-1 on HUVECs, as well as LOX-1, CD36, and CD162 on THP-1. Additionally, unoxidized LDL was exposed to the three breast cancer cell lines for 48 h, and the formation of oxLDL was quantified. Our results revealed an upregulation of all six adhesion markers involved in the initiation of atherosclerosis when HUVECs and THP-1 were exposed to the breast-cancer-conditioned medium. Furthermore, this expression was further increased by exposure to oxLDL. We also observed a significant elevation in oxLDL levels when LDL was exposed to breast cancer cells. In conclusion, our findings successfully demonstrate an increased LDL oxidation in the presence of breast cancer cells, accompanied by an augmented expression of receptors involved in atherosclerosis initiation. These findings shed new light on the clinically observed interplay between atherosclerosis and cancer.
心血管疾病是全球主要死因，紧随其后的是癌症。为了研究乳腺癌细胞系（SKBR3、MCF-7和MDA-MB-231）对内皮细胞黏附的影响，制备了一种含有30%乳腺癌条件培养基的混合培养基。然后将该培养基与人脐静脉内皮细胞（HUVECs）和单核细胞（THP-1）共培养48小时。混合培养基中可选择添加自制氧化低密度脂蛋白（oxLDL）。采用免疫荧光法评估HUVECs上E-选择素、连接蛋白-43和细胞间黏附分子-1（ICAM-1）以及THP-1上凝集素样氧化低密度脂蛋白受体-1（LOX-1）、CD36和CD162的表达。此外，将未氧化的低密度脂蛋白（LDL）与三种乳腺癌细胞系共培养48小时，并对oxLDL的形成进行定量分析。我们的结果显示，当HUVECs和THP-1暴露于乳腺癌条件培养基时，参与动脉粥样硬化起始的所有六种黏附标志物均上调。此外，暴露于oxLDL后，这种表达进一步增加。我们还观察到，当LDL暴露于乳腺癌细胞时，oxLDL水平显著升高。总之，我们的研究结果成功证明，在存在乳腺癌细胞的情况下，LDL氧化增加，同时参与动脉粥样硬化起始的受体表达增强。这些发现为临床上观察到的动脉粥样硬化与癌症之间的相互作用提供了新的线索。
