INHIBITION OF LUNG METASTASIS BY SYNTHETIC AND RECOMBINANT FRAGMENTS OF HUMAN FIBRONECTIN WITH FUNCTIONAL DOMAINS
INHIBITION OF LUNG METASTASIS BY SYNTHETIC AND RECOMBINANT FRAGMENTS OF HUMAN FIBRONECTIN WITH FUNCTIONAL DOMAINS
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DOI：
10.1111/j.1349-7006.1990.tb03338.x
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发表时间：
1990-10-01
期刊：
影响因子：
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通讯作者：
AZUMA, I
中科院分区：
文献类型：
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作者：
SAIKI, I;MURATA, J;AZUMA, I
我们研究了含有纤连蛋白功能域的合成或重组肽对小鼠肿瘤细胞的实验性和自发性肺转移的抗转移作用。当与 B16-BL6 黑色素瘤细胞静脉注射 (iv) 时，存在于 III 型同源连接段 (IIICS) 内的 CS1 肽以及 C-274（细胞结合结构域）能够抑制实验性肺转移，而 H-271（肝素结合结构域）则不能。在自发转移模型中，手术切除原发性肿瘤后多次静脉注射CS1或C-274导致肺部转移集落显着减少。当在溶液中自由添加时，CS1 和 C-274 均显着抑制细胞粘附和迁移到纤连蛋白包被的基质上。 CS1肽还抑制细胞对层粘连蛋白包被的基质的粘附和迁移，但C-274则没有。H-271对细胞对任一基质的粘附或迁移没有任何抑制作用。类似地，CS1抑制肿瘤对基质胶/纤连蛋白和基质胶/层粘连蛋白包被的滤膜的侵袭，而C-274仅抑制对基质胶/纤连蛋白包被的滤膜的侵袭。这些结果表明，缺乏含精氨酸-甘氨酸-天冬氨酸结构域的纤连蛋白的CS1肽在自发性和实验性转移模型中积极抑制肿瘤转移。这种肽的使用可能为对抗或预防癌症转移提供一种有前途的治疗方法。
We have investigated the antimetastatic effect of synthetic or recombinant peptides containing the functional domains of fibronectin on experimental and spontaneous lung metastases of murine tumor cells. CS1 peptide which is present within type III homology connecting segment (IIICS) as well as C-274 (cell-binding domain) were able to inhibit experimental lung metastasis when co-injected intravenously (iv) with B16-BL6 melanoma cells, while H-271 (heparin-binding domain) could not. In the spontaneous metastasis model, multiple iv administrations of CS1 or C-274 after surgical excision of primary tumors caused a significant reduction of metastatic colonies in the lung. Both CS1 and C-274 significantly inhibited cell adhesion and migration to fibronectin-coated substrates when added freely in solution. CS1 peptide also inhibited the cell adhesion and migration to laminin-coated substrates, but C-274 did not H. H-271 did not have any inhibitory effect on cell adhesion or migration to either of the substrates. Similarly, CS1 inhibited tumor invasion to both Matrigel/fibronectin- and Matrigel/laminin-coated filters, whereas C-274 inhibited the invasion to only Matrigel/fibronectin-coated filter. These results indicate that CS1 peptide of fibronectin, lacking the Arg-Gly-Asp-containing domain, actively inhibits tumor metastases in spontaneous and experimental metastasis models. The use of such a peptide might offer a promising therapeutic approach for combatting or preventing cancer metastasis.