Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 446K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schwarz, M. A. Articles by Stern, D. Search for Related Content PubMed PubMed Citation Articles by Schwarz, M. A. Articles by Stern, D. Social Bookmarking                            What's this?

Original Article

^a From the Department of Pediatrics, Department of Physiology, and the Department of Surgery, Columbia University, College of Physicians and Surgeons, New York 10032
^b Department of Pediatrics and the Department of Surgery, Childrens Hospital of Los Angeles, University of Southern California, Los Angeles, California 90027
^c Genentech, Inc., South San Francisco, California 94080
^d Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York 10021
^e Unité d'Immunohematologie, Laboratoire de Recherche en Biologie Vasculaire et Cellulaire, Université Paris 7, 75475 Paris, France
Departments of Pediatrics and Surgery, Children's Hospital Los Angeles, 4650 Sunset Blvd. MS #66, Los Angeles, CA 90027.323-913-2865323-669-4148

mschwarz{at}chla.usc.edu

Neovascularization is essential for growth and spread of primary and metastatic tumors. We have identified a novel cytokine, endothelial-monocyte activating polypeptide (EMAP) II, that potently inhibits tumor growth, and appears to have antiangiogenic activity. Mice implanted with Matrigel showed an intense local angiogenic response, which EMAP II blocked by 76% (P < 0.001). Neovascularization of the mouse cornea was similarly prevented by EMAP II (P < 0.003). Intraperitoneally administered EMAP II suppressed the growth of primary Lewis lung carcinomas, with a reduction in tumor volume of 65% versus controls (P < 0.003). Tumors from human breast carcinoma–derived MDA-MB 468 cells were suppressed by >80% in EMAP II–treated animals (P < 0.005). In a lung metastasis model, EMAP II blocked outgrowth of Lewis lung carcinoma macrometastases; total surface metastases were diminished by 65%, and of the 35% metastases present, 80% were inhibited with maximum diameter <2 mm (P < 0.002 vs. controls). In growing capillary endothelial cultures, EMAP II induced apoptosis in a time- and dose-dependent manner, whereas other cell types were unaffected. These data suggest that EMAP II is a tumor-suppressive mediator with antiangiogenic properties allowing it to target growing endothelium and limit establishment of neovasculature.

Key Words: tumor • capillary endothelium • programmed cell death • cell growth inhibitors • blood vessels

R. Schwarz's current address is Department of General Oncologic Surgery, City of Hope National Medical Center, 1500 East Duarte Rd., Duarte, CA 91010.

© 1999 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS