From the College of Pharmacy.
Department of Biological Science, Jining Medical University, Rizhao, China.
Pancreas. 2023 Jan 1;52(1):e29-e36. doi: 10.1097/MPA.0000000000002211.
The past studies clearly indicated that lumican was important in the context of pancreatic cancer (PC) onset and progression, but failed to clarify the underlying mechanistic basis for such activity. As such, we evaluated the functional importance of lumican in the context of pancreatic ductal adenocarcinoma (PDAC) to understand its mechanistic role in PC.
Lumican levels were evaluated in PDAC patient tissues via quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry approaches. The role of lumican was additionally assessed via transfecting PDAC cell lines (BxPC-3, PANC-1) with lumican knockdown or overexpression constructs and treating PDAC cell lines with exogenous recombinant human lumican.
Lumican expression levels were significantly higher in pancreatic tumor tissues relative to healthy paracancerous tissues. Lumican knockdown in BxPC-3 and PANC-1 enhanced their proliferation and migration, but reduced cellular apoptosis. Alternatively, lumican overexpression and exogenous lumican exposure failed to alter the proliferative activity of these cells. Further, lumican knockdown in BxPC-3 and PANC-1 cells results in marked P53 and P21 dysregulation.
Lumican may suppress PDAC tumor growth by regulating P53 and P21, and the function of lumican sugar chains in the context of PC is worth studying in future studies.
过去的研究清楚地表明,亮氨酸丰富糖蛋白在胰腺癌(PC)的发生和进展中具有重要作用,但未能阐明其这种活性的潜在机制基础。因此,我们评估了亮氨酸丰富糖蛋白在胰腺导管腺癌(PDAC)中的功能重要性,以了解其在 PC 中的机制作用。
通过实时定量聚合酶链反应、Western 印迹和免疫组织化学方法评估 PDAC 患者组织中的亮氨酸丰富糖蛋白水平。通过用亮氨酸敲低或过表达构建体转染 PDAC 细胞系(BxPC-3、PANC-1)并对外源重组人亮氨酸处理 PDAC 细胞系来评估亮氨酸的作用。
与健康癌旁组织相比,胰腺肿瘤组织中的亮氨酸丰富糖蛋白表达水平显著升高。BxPC-3 和 PANC-1 中的亮氨酸敲低增强了它们的增殖和迁移,但减少了细胞凋亡。相反,亮氨酸过表达和外源性亮氨酸暴露未能改变这些细胞的增殖活性。此外,BxPC-3 和 PANC-1 细胞中的亮氨酸敲低导致 P53 和 P21 明显失调。
亮氨酸可能通过调节 P53 和 P21 来抑制 PDAC 肿瘤生长,亮氨酸糖链在 PC 中的功能值得在未来的研究中进一步研究。