AJP - GI Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol 292: G223-G230, 2007. First published August 17, 2006; doi:10.1152/ajpgi.00259.2006
0193-1857/07 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/1/G223    most recent
00259.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Künzli, B. M.
Right arrow Articles by Robson, S. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Künzli, B. M.
Right arrow Articles by Robson, S. C.

LIVER AND BILIARY TRACT

Upregulation of CD39/NTPDases and P2 receptors in human pancreatic disease

Beat M. Künzli,1,2 Pascal O. Berberat,2 Thomas Giese,3 Eva Csizmadia,1 Elzbieta Kaczmarek,1 Colin Baker,1 Irfan Halaceli,2 Markus W. Büchler,2 Helmut Friess,2 and Simon C. Robson1

1Liver and Transplantation Centers, Beth Israel Deaconess Medical Center, Harvard University, Boston, Massachusetts; 2Department of General Surgery, University of Heidelberg, Heidelberg, Germany; and 3Institute of Immunology, University of Heidelberg, Heidelberg, Germany

Submitted 13 June 2006 ; accepted in final form 14 August 2006

Chronic inflammation, fibrosis, atrophy, malignant transformation, and thromboembolic events are hallmarks of chronic pancreatic disease. Extracellular nucleotides have been implicated as inflammatory mediators in many pathological situations. However, there are minimal data detailing expression of ectonucleotidases and type-2 purinergic receptors (P2R) in chronic pancreatitis and pancreatic cancer. We have therefore defined tissue distribution and localization of the CD39 family of ectonucleotidases and associated P2R in human disease. Transcripts of ectonucleotidases (CD39 and CD39L1) together with P2R (P2X7, P2Y2, and P2Y6) are significantly increased in both chronic pancreatitis and pancreatic cancer. CD39 and CD39L1 are preferentially associated with the vasculature and stromal elements in pathological tissues. P2X7 mRNA upregulation was associated with chronic pancreatitis, and heightened protein expression was found to be localized to infiltrating cells. P2Y2 was markedly upregulated in biopsies of pancreatic cancer tissues and expressed by fibroblasts adjacent to tumors. High-tissue mRNA levels of CD39 significantly correlated with better long-term survival after tumor resection in patients with pancreatic cancer. Heightened expression patterns and localization patterns of CD39, P2X7, and P2Y2 infer associations with chronic inflammation and neoplasia of the pancreas. Our data suggest distinct roles for CD39 and P2-purinergic signaling in both tissue remodeling and fibrogenesis with respect to human pancreatic diseases.

type-2 purinergic receptors; chronic pancreatitis; pancreatic cancer; pancreas


Address for reprint requests and other correspondence: S. C. Robson, Beth Israel Deaconess Medical Center, Dept. of Gastroenterology, Harvard Univ., Research North, Rm. 301, 99 Brookline Ave., Boston, MA 02215 (e-mail: srobson{at}bidmc.harvard.edu)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.