کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2130311 | 1086550 | 2014 | 15 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: SULF1/SULF2 splice variants differentially regulate pancreatic tumour growth progression SULF1/SULF2 splice variants differentially regulate pancreatic tumour growth progression](/preview/png/2130311.png)
• The onset of SULF1/SULF2 expression is an early marker of risk factor for tumorigenesis.
• SULF1/SULF2 expression in stroma is a prognostic marker of later stage cancer.
• SULF1/SULF2 variants differentially regulate in vitro and in vivo tumour growth.
• Specific SULF1/SULF2 splice variants are thus potential therapeutic targets.
This study highlights the highly dynamic nature of SULF1/SULF2 splice variants in different human pancreatic cancers that regulate the activities of multiple cell signalling pathways in development and disease. Most pancreatic tumours expressed variable levels of both SULF1 and SULF2 variants including some expression during inflammation and pancreatitis. Many ductal and centro-acinar cell-derived pancreatic tumours are known to evolve into lethal pancreatic ductal adenocarcinomas but the present study also detected different stages of such tumour progression in the same tissue biopsies of not only acinar cell origin but also islet cell-derived cancers. The examination of caerulein-induced pancreatic injury and tumorigenesis in a Kras-driven mouse model confirmed the activation and gradual increase of SULF1/SULF2 variants during pancreatitis and tumorigenesis but with reduced levels in Stat3 conditional knockout mice with reduced inflammation. The significance of differential spatial and temporal patterns of specific SULF1/SULF2 splice variant expression during cancer growth became further apparent from their differential stimulatory or inhibitory effects on growth factor activities, tumour growth and angiogenesis not only during in vitro but also in vivo growth thus providing possible novel therapeutic targets.
Journal: Experimental Cell Research - Volume 324, Issue 2, 10 June 2014, Pages 157–171