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