Endothelial-monocyte activating polypeptide II, a novel antitumor cytokinethat suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells

Citation
Ma. Schwarz et al., Endothelial-monocyte activating polypeptide II, a novel antitumor cytokinethat suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells, J EXP MED, 190(3), 1999, pp. 341-353
Citations number
51
Categorie Soggetti
Medical Research General Topics
Journal title
JOURNAL OF EXPERIMENTAL MEDICINE
ISSN journal
00221007 → ACNP
Volume
190
Issue
3
Year of publication
1999
Pages
341 - 353
Database
ISI
SICI code
0022-1007(19990802)190:3<341:EAPIAN>2.0.ZU;2-Q
Abstract
Neovascularization is essential for growth and spread of primary and metast atic tumors. We have identified a novel cytokine, endothelial-monocyte acti vating polypeptide (EMAP) II, that potently inhibits tumor growth, and appe ars 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 I I (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 carc inoma macrometastases; total surface metastases were diminished by 65%, and of the 35% metastases present, approximate to 80% were inhibited with maxi mum diameter <2 mm (P < 0.002 vs. controls). In growing capillary endotheli al 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.