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

Margaret A. Schwarz, Jessica Kandel, Jerald Brett, Jun Li, Joanne Hayward, Roderich E. Schwarz, Olivier Chappey, Jean Luc Wautier, John Chabot, Paul Lo Gerfo, David Stern

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)341-353
Number of pages13
JournalJournal of Experimental Medicine
Volume190
Issue number3
DOIs
StatePublished - Aug 2 1999

Keywords

  • Blood vessels
  • Capillary endothelium
  • Cell growth inhibitors
  • Programmed cell death
  • Tumor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Schwarz, M. A., Kandel, J., Brett, J., Li, J., Hayward, J., Schwarz, R. E., Chappey, O., Wautier, J. L., Chabot, J., Lo Gerfo, P., & Stern, D. (1999). Endothelial-monocyte activating polypeptide II, a novel antitumor cytokine that suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells. Journal of Experimental Medicine, 190(3), 341-353. https://doi.org/10.1084/jem.190.3.341