Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Oncogene ; 36(30): 4288-4298, 2017 07 27.
Article in English | MEDLINE | ID: mdl-28346421

ABSTRACT

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2-/- mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer.


Subject(s)
Carcinoma, Pancreatic Ductal/pathology , Pancreatic Neoplasms/pathology , Plasminogen Activator Inhibitor 2/metabolism , Tumor Microenvironment , Animals , Carcinoma, Pancreatic Ductal/metabolism , Fibroblasts/metabolism , Fibroblasts/pathology , Gene Expression Profiling , Humans , Mice , Microscopy, Electron, Scanning , Pancreatic Neoplasms/metabolism , Transcriptome
SELECTION OF CITATIONS
SEARCH DETAIL
...