Tsaur Igor, Thomas Anita, Juengel Eva, Maxeiner Sebastian, Grein Timothy, Le Quynh Chi, Muschta Veronika, Rutz Jochen, Chun Felix K H, Blaheta Roman A
Department of Urology and Pediatric Urology, University Medicine Mainz, 55131 Mainz, Germany.
Department of Urology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt, Germany.
Biology (Basel). 2021 Oct 7;10(10):1007. doi: 10.3390/biology10101007.
The serum level of soluble (s)E-cadherin is elevated in several malignancies, including prostate cancer (PCa). This study was designed to investigate the effects of sE-cadherin on the behavior of PCa cells in vitro, with the aim of identifying a potential therapeutic target. Growth as well as adhesive and motile behavior were evaluated in PC3, DU-145, and LNCaP cells. Flow cytometry was used to assess cell cycle phases and the surface expression of CD44 variants as well as α and β integrins. Confocal microscopy was utilized to visualize the distribution of CD44 variants within the cells. Western blot was applied to investigate expression of α3 and β1 integrins as well as cytoskeletal and adhesion proteins. Cell growth was significantly inhibited after exposure to 5 µg/mL sE-cadherin and was accompanied by a G0/G1-phase arrest. Adhesion of cells to collagen and fibronectin was mitigated, while motility was augmented. CD44v4, v5, and v7 expression was elevated while α3 and β1 integrins were attenuated. Blocking integrin α3 reduced cell growth and adhesion to collagen but increased motility. sE-cadherin therefore appears to foster invasive tumor cell behavior, and targeting it might serve as a novel and innovative concept to treat advanced PCa.
可溶性(s)E-钙黏蛋白的血清水平在包括前列腺癌(PCa)在内的多种恶性肿瘤中升高。本研究旨在探讨sE-钙黏蛋白对PCa细胞体外行为的影响,以确定潜在的治疗靶点。对PC3、DU-145和LNCaP细胞的生长以及黏附与运动行为进行了评估。采用流式细胞术评估细胞周期阶段以及CD44变体和α及β整合素的表面表达。利用共聚焦显微镜观察细胞内CD44变体的分布。应用蛋白质免疫印迹法研究α3和β1整合素以及细胞骨架和黏附蛋白的表达。暴露于5μg/mL的sE-钙黏蛋白后,细胞生长受到显著抑制,并伴有G0/G1期阻滞。细胞与胶原蛋白和纤连蛋白的黏附减弱,而运动性增强。CD44v4、v5和v7的表达升高,而α3和β1整合素减弱。阻断整合素α3可降低细胞生长和对胶原蛋白的黏附,但增加运动性。因此,sE-钙黏蛋白似乎促进了肿瘤细胞的侵袭行为,针对它可能是治疗晚期PCa的一种新颖且创新的理念。