Clinical Cancer Research The Science of Cancer Health Disparities
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Watanabe, Y.
Right arrow Articles by Mizutani, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Watanabe, Y.
Right arrow Articles by Mizutani, S.
Related Collections
Right arrowCommentary
Clinical Cancer Research Vol. 9, 6497-6503, December 15, 2003
© 2003 American Association for Cancer Research


Experimental Therapeutics, Preclinical Pharmacology

Adipocyte-Derived Leucine Aminopeptidase Suppresses Angiogenesis in Human Endometrial Carcinoma via Renin-Angiotensin System

Yoshiteru Watanabe1, Kiyosumi Shibata1, Fumitaka Kikkawa1, Hiroaki Kajiyama1, Kazuhiko Ino1, Akira Hattori2, Masafumi Tsujimoto2 and Shigehiko Mizutani1

1 Department of Obstetrics and Gynecology, Nagoya Graduate University School of Medicine, Nagoya, Japan, and
2 RIKEN (Laboratory of Cellular Biochemistry, Institute of Physical and Chemical Research), Saitama, Japan

Purpose: Angiotensin (Ang) II was reported to induce vascular endothelial growth factor (VEGF) expression in various cells. Adipocyte-derived leucine aminopeptidase (A-LAP) is a novel member of the M1 family of zinc metallopeptidases. Enzymatic characterization demonstrated that A-LAP hydrolyzes Ang II. This study examined the role of A-LAP in angiogenesis of human endometrial carcinoma.

Experimental Design: We investigated whether Ang II induces VEGF expression in human endometrial carcinoma cells. To investigate the possible function of A-LAP in angiogenesis of endometrial carcinoma, we transfected A-LAP cDNA into HEC-1A cells, showing the lowest expression of A-LAP.

Results: In the present study, we showed that Ang II enhanced VEGF expression in a dose-dependent manner in endometrial carcinoma cells (HEC-1A cells). Overexpression of A-LAP attenuated Ang II-induced VEGF expression in HEC-1A cells. In addition, Human umbilical vascular endothelial cell migration was increased in conditioned media from Ang II-treated wild-type cells, but not in conditioned media from Ang II-treated A-LAP-overexpressing cells (HEC-1A-A-LAP cells). In an in vivo study, we showed that A-LAP overexpression in endometrial carcinoma cells results in a reduction of VEGF immunoreactivity and the number of blood vessels within tumors.

Conclusions: Our study demonstrates that it is feasible to overexpress Ang II-degrading enzymes in cultured cells and that this overexpression attenuated some effects of exogenous and endogenous Ang II. These experiments are a first step toward the development of novel strategies to selectively antagonize locally generated Ang II and suppress VEGF-induced angiogenesis in endometrial carcinoma.


Commentary

Of Peptides and Peptidases: The Role of Cell Surface Peptidases in Cancer
David M. Nanus
Clin. Cancer Res. 2003 9: 6307-6309. [Full Text] [PDF]






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2003 by the American Association for Cancer Research.