JQ1 effectively inhibits vasculogenic mimicry of pancreatic ductal adenocarcinoma cells via the ERK1/2-MMP-2/9 signaling pathway both in vitro and in vivo

American Journal of Translational Research

Ting Han¹  Meng Zhuo²  Cuncun Yuan³ 

[1] Department of Medical Oncology and Pancreatic Cancer Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China;Department of Oncology, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Cancer Institute, Shanghai 200127, China;Department of Pathology, Eye ENT Hospital of Fudan University, 83 Fenyang Road, Shanghai 201114, P. R. China

关键词: Pancreatic ductal adenocarcinoma;    vasculogenic mimicry;    JQ1;    ERK1/2;    MMP-2/9;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Vasculogenic mimicry (VM) is an alternative type of blood and nutrition supply that is associated with more aggressive tumor biology and increased cancer-related mortality. However, the clinical implications of VM remain unclear in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the clinical significance of VM in PDAC patients and to seek a novel and more efficient treatment strategy by targeting this unique process. Here, cluster of differentiation 34 (CD34)/periodic acid-Schiff (PAS) double-staining of 76 PDAC clinical specimens revealed that VM expression was related to clinical stage (P=0.049) and lymph node metastasis (P=0.023). Notably, VM expression was correlated with a poor prognosis in patients with PDAC. Additionally, we discovered that there was a positive correlation between the expressions of VM and phosphorylated extracellular signal regulated kinase (p-ERK1/2) in 76 clinical samples (P<0.001). Moreover, our results further indicated that treatment with the ERK1/2 inhibitor SCH772984 effectively blocked VM formation by repressing the production of p-ERK1/2-MMP-2/9, which have been established as classical markers of VM. Further, JQ1, a bromodomain and extraterminal domain (BET) inhibitor, also exerted significant inhibitory efficiency against VM formation by decreasing the activation of ERK1/2-MMP-2/9. In conclusion, our work suggests that VM is a marker of poor prognosis in patients with PDAC and that JQ1 can inhibit VM formation via the ERK1/2-MMP-2/9 signaling pathway.

【 授权许可】

CC BY-NC