人羊膜通过下调 FAK/PI3K/Akt/mTOR 信号通路抑制肌层浸润性膀胱癌尿路上皮细胞的迁移和侵袭。
Human amniotic membrane inhibits migration and invasion of muscle-invasive bladder cancer urothelial cells by downregulating the FAK/PI3K/Akt/mTOR signalling pathway.
发表日期:2023 Nov 06
作者:
Aleksandar Janev, Taja Železnik Ramuta, Urška Dragin Jerman, Hristina Obradović, Urška Kamenšek, Maja Čemažar, Mateja Erdani Kreft
来源:
Cellular & Molecular Immunology
摘要:
膀胱癌是第十大最常诊断的癌症,其终生治疗费用最高。人羊膜(hAM)是最内层的胎儿膜,具有广泛的生物学特性,包括抗炎、抗菌和抗癌特性。尽管研究数量不断增加,但与人羊膜 (hAM) 抗癌作用相关的机制仍知之甚少。在这里,我们报道了 hAM 制剂(匀浆和提取物)以剂量依赖性方式抑制膀胱癌尿路上皮细胞中上皮间质转化标志物 N-钙粘蛋白和 MMP-2 的表达,同时增加 TIMP-2 的分泌。此外,hAM匀浆通过下调FAK和参与肌动蛋白细胞骨架重组的蛋白质(例如皮质素和小RhoGTP酶)的表达来发挥其抗迁移作用。在肌肉浸润性癌尿路上皮细胞中,hAM 匀浆下调 PI3K/Akt/mTOR 信号通路,这是促进膀胱癌的关键级联反应。通过使用正常的非浸润性乳头状瘤和肌肉浸润性癌症尿路上皮模型,hAM 的抗癌作用出现了新的观点。结果确定了治疗干预的新位点,并及时鼓励了正在进行的抗癌药物开发研究。© 2023。作者。
Bladder cancer is the 10th most commonly diagnosed cancer with the highest lifetime treatment costs. The human amniotic membrane (hAM) is the innermost foetal membrane that possesses a wide range of biological properties, including anti-inflammatory, antimicrobial and anticancer properties. Despite the growing number of studies, the mechanisms associated with the anticancer effects of human amniotic membrane (hAM) are poorly understood. Here, we reported that hAM preparations (homogenate and extract) inhibited the expression of the epithelial-mesenchymal transition markers N-cadherin and MMP-2 in bladder cancer urothelial cells in a dose-dependent manner, while increasing the secretion of TIMP-2. Moreover, hAM homogenate exerted its antimigratory effect by downregulating the expression of FAK and proteins involved in actin cytoskeleton reorganisation, such as cortactin and small RhoGTPases. In muscle-invasive cancer urothelial cells, hAM homogenate downregulated the PI3K/Akt/mTOR signalling pathway, the key cascade involved in promoting bladder cancer. By using normal, non-invasive papilloma and muscle-invasive cancer urothelial models, new perspectives on the anticancer effects of hAM have emerged. The results identify new sites for therapeutic intervention and are prompt encouragement for ongoing anticancer drug development studies.© 2023. The Author(s).