The suppression of cell motility through the reduction of FAK activity and expression of cell adhesion proteins by hAMSCs secretome in MDA-MB-231 breast cancer cells.

IF 3 3区 医学 Q2 ONCOLOGY
Investigational New Drugs Pub Date : 2024-06-01 Epub Date: 2024-03-27 DOI:10.1007/s10637-024-01434-2
Fatemeh Safari, Setareh Bararpour, Fatemeh Omidi Chomachaei
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引用次数: 0

Abstract

Breast cancer is a leading cause of death in women worldwide. Cancer therapy based on stem cells is considered as a novel and promising platform. In the present study, we explore the therapeutic effects of human amniotic mesenchymal stromal cells (hAMSCs) through the reduction of focal adhesion kinase (FAK) activity, SHP-2, and cell adhesion proteins such as Paxillin, Vinculin, Fibronectin, Talin, and integrin αvβ3 expression in MDA-MB-231 breast cancer cells. For this purpose, we employed a co-culture system using 6-well plate transwell. After 72 h, hAMSCs-treated MDA-MB-231 breast cancer cells, the activity of focal adhesion kinase (FAK) and the expression of SHP-2 and cell adhesion proteins such as Paxillin, Vinculin, Fibronectin, Talin, and integrin αvβ3 expression were analyzed using western blot. The shape and migration of cells were also analyzed. Based on our results, a significant reduction in tumor cell motility through downregulation of the tyrosine phosphorylation level of FAK (at Y397 and Y576/577 sites) and cell adhesion expression in MDA-MB-231 breast cancer cells was demonstrated. Our findings indicate that hAMSCS secretome has therapeutic effects on cancer cell migration through downregulation of FAK activity and expression of cell adhesion proteins.

hAMSCs 分泌组通过降低 MDA-MB-231 乳腺癌细胞中 FAK 的活性和细胞粘附蛋白的表达来抑制细胞的运动性。
乳腺癌是全球妇女的主要死因。以干细胞为基础的癌症疗法被认为是一种新颖而有前景的平台。在本研究中,我们探讨了人羊膜间充质基质细胞(hAMSCs)通过降低MDA-MB-231乳腺癌细胞中局灶粘附激酶(FAK)活性、SHP-2和细胞粘附蛋白(如Paxillin、Vinculin、Fibronectin、Talin和整合素αvβ3的表达)的治疗效果。为此,我们采用了6孔板Transwell共培养系统。经 hAMSCs 处理的 MDA-MB-231 乳腺癌细胞 72 h 后,用 Western 印迹法分析了病灶粘附激酶(FAK)的活性、SHP-2 的表达以及 Paxillin、Vinculin、Fibronectin、Talin 等细胞粘附蛋白和整合素 αvβ3 的表达。此外,还分析了细胞的形状和迁移。结果表明,通过下调 FAK 的酪氨酸磷酸化水平(Y397 和 Y576/577 位点)和细胞粘附表达,MDA-MB-231 乳腺癌细胞的肿瘤细胞运动能力显著降低。我们的研究结果表明,hAMSCS 分泌组通过下调 FAK 活性和细胞粘附蛋白的表达,对癌细胞迁移具有治疗作用。
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来源期刊
CiteScore
7.60
自引率
0.00%
发文量
121
审稿时长
1 months
期刊介绍: The development of new anticancer agents is one of the most rapidly changing aspects of cancer research. Investigational New Drugs provides a forum for the rapid dissemination of information on new anticancer agents. The papers published are of interest to the medical chemist, toxicologist, pharmacist, pharmacologist, biostatistician and clinical oncologist. Investigational New Drugs provides the fastest possible publication of new discoveries and results for the whole community of scientists developing anticancer agents.
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