Department of Hepatopancreatobiliary, Third Affiliated Hospital of Soochow University, Changzhou 213001, China.
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Acta Biochim Biophys Sin (Shanghai). 2023 Jun 19;55(9):1393-1403. doi: 10.3724/abbs.2023118.
Since the prognosis of patients with pancreatic cancer is very poor and there is a lack of treatment methods, this study is performed to investigate the function of PITX2 in pancreatic stellate cells (PSCs) in the progression of pancreatic cancer. Scientific hypotheses are proposed according to bioinformatics analysis and tissue microarray analysis. Stable knockdown of in PSCs is achieved through lentiviral infection. The relative expressions of PITX2, α-SMA, vimentin, CTNNB1, AXIN1 and LEF1 are measured in wild-type PSCs and -knockdown PSCs. Proliferative capacity is measured by EdU assay. After coculture with PSCs, the proliferation, invasion and migration capacity of pancreatic cancer cells are tested. EMT and Wnt/β-catenin downstream genes of pancreatic cancer cells are investigated to reveal the potential mechanism. Bioinformatics analysis reveals that the gene is highly expressed in stromal cells in pancreatic cancer and is correlated with squamous-type PDAC. Analysis of PDAC tissue microarray further demonstrates that high PITX2 level in stromal cells is correlated with poor prognosis in PDAC. After stable knockdown of in PSCs, the relative protein levels of α-SMA, vimentin, CTNNB1, AXIN1 and LEF1 are decreased, and the proliferative capacity of PSCs is also decreased. After coculture with PSCs, in which PITX2 expression is downregulated, the proliferation, invasion and migration capacities of pancreatic cancer cells are inhibited. Thus, our results show that -silenced PSCs inhibit the growth, migration and invasion of pancreatic cancer cells via reduced EMT and Wnt/β-catenin signaling.
由于胰腺癌患者的预后非常差，并且缺乏治疗方法，因此进行了这项研究，以探讨胰腺星状细胞（PSC）中 PITX2 在胰腺癌进展中的作用。根据生物信息学分析和组织微阵列分析提出科学假设。通过慢病毒感染实现 PSCs 中 的稳定敲低。在野生型 PSCs 和 -敲低 PSCs 中测量 PITX2、α-SMA、波形蛋白、CTNNB1、AXIN1 和 LEF1 的相对表达。通过 EdU 测定测量增殖能力。与 PSCs 共培养后，测试胰腺癌细胞的增殖、侵袭和迁移能力。研究胰腺癌细胞的 EMT 和 Wnt/β-catenin 下游基因，以揭示潜在的机制。生物信息学分析表明， 基因在胰腺癌中的基质细胞中高表达，与鳞状型 PDAC 相关。对 PDAC 组织微阵列的进一步分析表明，基质细胞中高 PITX2 水平与 PDAC 的不良预后相关。在 PSCs 中稳定敲低 后，α-SMA、波形蛋白、CTNNB1、AXIN1 和 LEF1 的相对蛋白水平降低，PSC 的增殖能力也降低。与下调 PITX2 表达的 PSCs 共培养后，胰腺癌细胞的增殖、侵袭和迁移能力受到抑制。因此，我们的结果表明，沉默的 PSCs 通过减少 EMT 和 Wnt/β-catenin 信号通路来抑制胰腺癌细胞的生长、迁移和侵袭。
