Endothelial-monocyte activating polypeptide II, a novel antitumor cytokine that suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells Journal Article
| Authors: | 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. |
| Article Title: | Endothelial-monocyte activating polypeptide II, a novel antitumor cytokine that suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells |
| 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. |
| Keywords: | controlled study; unclassified drug; human cell; angiogenesis inhibitor; nonhuman; animal cell; mouse; animals; mice; animal tissue; cells, cultured; cell division; metastasis; apoptosis; tumor volume; neoplasm proteins; animal experiment; cancer cell culture; tumor cells, cultured; mice, inbred balb c; endothelium cell; fibroblast growth factor 2; rna-binding proteins; cancer inhibition; cytokine; cytokines; tissue distribution; endothelium, vascular; mice, nude; breast carcinoma; recombinant proteins; cattle; tumor; neovascularization, physiologic; infusions, intravenous; neovascularization (pathology); lewis carcinoma; blood vessels; growth inhibitors; carcinoma, lewis lung; capillary endothelium; programmed cell death; humans; human; priority journal; article; cell growth inhibitors; endothelial monocyte activating polypeptide ii; recombinant endothelial monocyte activating polypeptide ii |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 190 |
| Issue: | 3 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 1999-08-02 |
| Start Page: | 341 |
| End Page: | 353 |
| Language: | English |
| DOI: | 10.1084/jem.190.3.341 |
| PUBMED: | 10430623 |
| PROVIDER: | scopus |
| PMCID: | PMC2195582 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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