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A more recent version of this article appeared on June 1, 2007

Published online before print April 19, 2007
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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.060935


Accepted for publication March 14, 2007.


Article

Enhanced Expression of Keratinocyte Growth Factor and Its Receptor Correlates with Venous Invasion in Pancreatic Cancer

Kazumitsu Cho*{dagger}, Toshiyuki Ishiwata{dagger}, Eiji Uchida*, Nando Nakazawa{dagger}, Murray Korc{ddagger}, Zenya Naito{dagger}@, and Takashi Tajiri*

From the Department of Surgery* and the Department of Integrative Pathology, Department of Pathology II,{dagger} Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; and the Department of Medicine,{ddagger} Dartmouth Medical School and Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire

@ To whom correspondence should be addressed. E-mail: naito{at}nms.ac.jp.


   Abstract

Keratinocyte growth factor (KGF) and KGF receptor (KGFR) have been implicated in cancer growth as well as tissue development and repair. In this study, we examined whether KGF and KGFR have a role in human pancreatic ductal adenocarcinoma (PDAC). KGFR mRNA was expressed in eight pancreatic cancer cell lines, whereas the KGF mRNA was detected in seven of the cell lines and was absent in MIA PaCa-2 cells. KGFR and KGF immunoreactivity were localized in the cancer cells in 41.5 and 34.0% of patients, respectively. There was a significant correlation between KGFR or KGF immunoreactivity and venous invasion and a significant correlation between the presence of both markers and venous invasion, vascular endothelial growth factor (VEGF)-A expression, and poor prognosis. Exogenous KGF increased VEGF-A expression and release in MIA PaCa-2 cells, and PANC-1 cells stably transfected to overexpress KGF-exhibited increased VEGF-A expression. Moreover, short hairpin-KGFR transfection in MIA PaCa-2 cells reduced the stimulatory effect of exogenous KGF on VEGF-A expression. Short hairpin-KGF transfection in KLM-1 cells reduced VEGF-A expression in the cells. KGFR and KGF may act to promote venous invasion and tumor angiogenesis in PDAC, raising the possibility that they may serve as novel therapeutic targets in anti-angiogenic strategies in PDAC.








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Copyright © 2007 by the American Society for Investigative Pathology.