A fibronectin fragment inhibits tumor growth, angiogenesis, and metastasis
A fibronectin fragment inhibits tumor growth, angiogenesis, and metastasis
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DOI：
10.1073/pnas.98.2.620
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发表时间：
2001-01-16
影响因子：
11.1
通讯作者：
Ruoslahti, E
中科院分区：
文献类型：
--
作者：
Yi, M;Ruoslahti, E
我们以前已经证明，当全身给药给荷瘤小鼠时，一种聚合形式的纤维连接蛋白具有很强的抗肿瘤转移作用。聚合性纤维连接蛋白SFN是在体外用76-AA多肽III1-C处理可溶性纤维连接蛋白形成的，III1-C来源于纤维连接蛋白的第一类型III重复序列。在这里，我们显示了III1-C肽和SFN也减少了小鼠的肿瘤生长，并且这种效果与治疗小鼠肿瘤中的低血管密度有关。III1-C还聚合了纤维蛋白原，纤维蛋白原聚合物SFBG具有与SFN相似的抗肿瘤和抗血管生成作用。注射了S.C.的小鼠。用三种不同类型的人类肿瘤细胞，每两周一次，每天一次。在5周内注射III1-C、SFN或SFBG的小鼠肿瘤比对照组小50%-90%。实验结束时，治疗组小鼠的肿瘤血管密度降低了60-80%。来自人乳腺癌细胞系(MDA-MB-435)的异种移植瘤对这些治疗特别敏感。从原发灶转移到肺部。在用III1-C和这两种聚合物治疗的小鼠中，肿瘤也受到抑制。III1-C肽是一种抗血管生成和抗肿瘤转移的药物。由于其抑制肿瘤生长、血管生成和转移的能力，我们将III1-C多肽命名为Anastellin[源自anastello(希腊语)，Inhibit，Form a Case]。
We have shown previously that a polymeric form of fibronectin is strongly antimetastatic when administered systemically to tumor-bearing mice. The polymeric fibronectin, sFN, is formed in vitro by treating soluble fibronectin with a 76-aa peptide, III1-C which is derived from the first type III repeat in fibronectin. Here we show that the III1-C peptide and sFN also reduce tumor growth in mice, and that this effect correlates with a low density of blood vessels in the tumors of the treated mice. III1-C also polymerized fibrinogen, and the fibrinogen polymer, sFBG, had antitumor and antiangiogenic effects similar to those of sFN. Mice that had been injected s.c. with three different types of human tumor cells and treated with biweekly i.p. injections of III1-C, sFN, or sFBG over a 5-week period had tumors that were 50-90% smaller than those of control mice. Blood vessel density in the tumors of the treated mice was reduced by 60-80% at the end of the experiment. Xenograft tumors from a human breast carcinoma line (MDA-MB-435) were particularly susceptible to these treatments. Metastasis into the lungs from the primary s.c. tumors also was inhibited in the mice treated with III1-C and the two polymers. The III1-C peptide is an antiangiogenic and antimetastatic agent. Because of its ability to suppress tumor growth, angiogenesis, and metastasis, we have named the III1-C peptide anastellin [from anastello (Greek), inhibit, force a retreat].