Epithelial-to-mesenchymal transition predicts prognosis of pancreatic cancer

Yamada, Suguru; Fuchs, Bryan C.; Fujii, Tsutomu; Shimoyama, Yoshie; Sugimoto, Hiroyuki; Nomoto, Shuji; Takeda, Shin; Tanabe, Kenneth K.; Kodera, Yasuhiro; Nakao, Akimasa

doi:10.1016/j.surg.2013.05.004

Cited by 107 publications

(104 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings suggest that low expression of vimentin is related to well-differentiated tumors. These data are similar to those of the literature as vimentin expression is associated with an aggressive tumor phenotype (38)(39)(40). ECadherin and vimentin expression were not significantly associated with other clinicopathological parameters in this study.…”

Section: Discussionsupporting

confidence: 92%

Epithelial–Mesenchymal Transition in Non Small-cell Lung Cancer

2017

View full text Add to dashboard Cite

Abstract. Background/Aim: Lung cancer is the first cause of cancer related deaths in both males and females. Epithelialmesenchymal transition (EMT) is a reversible process by which epithelial cells transform to mesenchymal stem cells by losing their cell polarity and cell-to-cell adhesionLung cancer is the first cause of cancer-related deaths in both males and females. It is a fatal disease and most patients with lung cancer will die of their disease (1). Two main types of lung cancer exist: non-small-cell lung cancer (NSCLC) accounting for 85-90% of lung cancer cases, and small-cell lung cancer (SCLC), whose incidence seems to have decreased over the past decades (2). The current therapeutic approach for lung cancer includes surgical tumor removal, platinum-based chemotherapy, targeted therapy, immunotherapy and radiation therapy. Improvements in clinical and molecular understanding of the disease have resulted in novel therapeutic approaches. Multiple genetic and epigenetic abnormalities results in both oncogene activation [epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)] and inactivation of tumor-suppressor genes [transcription factor (p53) and retinoblastoma protein (RB)] (3). Moreover, angiogenesis seems to play an important role in the process of invasion and metastasis in lung cancer (4). Other molecular and cellular processes of lung cancer include genomic instability, escape from apoptosis, cell immortalization, abnormalities in immune response and epithelial-mesenchymal transition (EMT) (5-9).

show abstract

Section: Discussionsupporting

confidence: 92%

Epithelial–Mesenchymal Transition in Non Small-cell Lung Cancer

2017

View full text Add to dashboard Cite

show abstract

“…It has been shown to be prevalent in pancreatic ductal adenocarcinoma tissue and to negatively impact patient prognosis. 52 The potential functional link between collagen reorganization and increased pancreatic ductal adenocarcinoma cancer cell migration has yet to be elucidated. Another potential pathological consequence of collagen reorganization in pancreatic ductal adenocarcinoma is increased matrix tension.…”

Section: Discussionmentioning

confidence: 99%

Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis

et al. 2015

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma continues to be one of the most difficult diseases to manage with one of the highest cancer mortality rates. This is due to several factors including nonspecific symptomatology and subsequent diagnosis at an advanced stage, aggressive metastatic behavior that is incompletely understood, and limited response to current therapeutic regimens. As in other cancers, there is great interest in studying the role of the tumor microenvironment in pancreatic ductal adenocarcinoma and whether components of this environment could serve as research and therapeutic targets. In particular, attention has turned toward the desmoplastic collagen-rich pancreatic ductal adenocarcinoma stroma for both biological and clinical insight. In this study, we used quantitative second harmonic generation microscopy to investigate stromal collagen organization and structure in human pancreatic ductal adenocarcinoma pathology tissues compared with non-neoplastic tissues. Collagen topology was characterized in whole-tissue microarray cores and at specific pathology-annotated epithelial-stroma interfaces representing 241 and 117 patients, respectively. We quantitatively demonstrate that a unique collagen topology exists in the periductal pancreatic ductal adenocarcinoma stroma. Specifically, collagen around malignant ducts shows increased alignment, length, and width compared with normal ducts and benign ducts in a chronic pancreatitis background. These findings indicate that second harmonic generation imaging can provide quantitative information about fibrosis that complements traditional histopathologic insights and can serve as a rich field for investigation into pathogenic and clinical implications of reorganized collagen as a pancreatic ductal adenocarcinoma disease marker. Pancreatic ductal adenocarcinoma is one of the most devastating human malignancies. It is currently the fourth leading cause of cancer death and projects to become the second leading cause by 2030. 1 The 5-year relative survival rate has remained in the single digits for decades. Pancreatic ductal adenocarcinoma is notoriously difficult to detect before an advanced, inoperable stage is reached due to nonspecific symptomatology and the retroperitoneal location of the pancreas, which makes palpation or routine biopsy of suspicious masses difficult. Recent advances in the sensitivity and specificity of preoperative imaging modalities such as computer tomography, magnetic resonance imaging, positron emission tomography, endoscopic ultrasonography, and endoscopic retrograde cholangiopancreatography have played an important role in enhancing pancreatic ductal adenocarcinoma diagnosis, detailing the relationship of lesions to nearby anatomical structures, and determining the course of management. 2 Despite these advances, only 10-15% of patients are diagnosed at a localized disease stage when surgical resection is possible as a potential curative therapy. However, postsurgical recurrence rates are high with 5-year survival rate of

show abstract

“…Because low miR-192 correlated with shorter survival times, which is often due to metastasis, we examined the role of miR-192 in PDAC metastasis focusing on EMT, a predominant phenotype of tumor progression and invasiveness (20,21). To this end, we performed qRT-PCR analysis of miR-192 in five different pancreatic cancer cell lines of two different subtypes: cell lines that originated from primary pancreatic tumors (PANC-1, MIAPaCa-2, and BxPC-3) and cells from liver metastases (CAPAN-1 and CFPAC-1; Fig.…”

Section: Mir-192 Is Involved In the Emtmentioning

confidence: 99%

Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression

et al. 2016

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is characterized by very early metastasis, suggesting the hypothesis that metastasisassociated changes may occur prior to actual tumor formation. In this study, we identified miR-192 as an epigenetically regulated suppressor gene with predictive value in this disease. miR-192 was downregulated by promoter methylation in both PDAC and chronic pancreatitis, the latter of which is a major risk factor for the development of PDAC. Functional studies in vitro and in vivo in mouse models of PDAC showed that overexpression of miR-192 was sufficient to reduce cell proliferation and invasion. Mechanistic analyses correlated changes in miR-192 promoter methylation and expression with epithelial-mesenchymal transition. Cell proliferation and invasion were linked to altered expression of the miR-192 target gene SERPINE1 that is encoding the protein plasminogen activator inhibitor-1 (PAI-1), an established regulator of these properties in PDAC cells. Notably, our data suggested that invasive capacity was altered even before neoplastic transformation occurred, as triggered by miR-192 downregulation. Overall, our results highlighted a role for miR-192 in explaining the early metastatic behavior of PDAC and suggested its relevance as a target to develop for early diagnostics and therapy.

show abstract

Epithelial-to-mesenchymal transition predicts prognosis of pancreatic cancer

Cited by 107 publications

References 32 publications

Epithelial–Mesenchymal Transition in Non Small-cell Lung Cancer

Epithelial–Mesenchymal Transition in Non Small-cell Lung Cancer

Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis

Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression

Contact Info

Product

Resources

About