Endothelial-monocyte activating polypeptide II, a novel antitumor cytokine that suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells.
Endothelial-monocyte activating polypeptide II, a novel antitumor cytokine that suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells.
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DOI：
10.1084/jem.190.3.341
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发表时间：
1999-08-02
期刊：
影响因子：
--
通讯作者：
Stern D
中科院分区：
文献类型：
--
作者：
Schwarz MA;Kandel J;Brett J;Li J;Hayward J;Schwarz RE;Chappey O;Wautier JL;Chabot J;Lo Gerfo P;Stern D
新生血管对原发和转移性肿瘤的生长和扩散是必不可少的。我们已经确定了一种新的细胞因子，内皮-单核细胞激活多肽(EMAP)II，它可以有效地抑制肿瘤生长，并似乎具有抗血管生成活性。植入Matrigel的小鼠表现出强烈的局部血管生成反应，EMAP II阻断了76%(P<；0.001)。EMAP II类似地阻止了小鼠角膜的新生血管(P<；0.003)。腹腔注射EMAPII抑制了原发Lewis肺癌的生长，与对照组相比，肿瘤体积缩小了65%(P<；0.003)。在EMAP II处理的动物中，来自人乳腺癌来源的MDA-MB468细胞的肿瘤被>；80%抑制(P<；0.005)。在肺转移模型中，EMAP II阻止了Lewis肺癌大转移的生长；总的表面转移减少了65%，在存在的35%的转移中，≈80%被抑制，最大直径为2 mm(P<；0.002与对照组相比)。在生长的毛细血管内皮细胞培养中，EMAP II以时间和剂量依赖的方式诱导细胞凋亡，而其他类型的细胞不受影响。这些数据表明，EMAP II是一种肿瘤抑制介质，具有抗血管生成的特性，使其能够靶向生长的内皮细胞，并限制新生血管的建立。
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.