YIGSR, A SYNTHETIC LAMININ PEPTIDE, INHIBITS THE ENHANCEMENT BY CYCLOPHOSPHAMIDE OF EXPERIMENTAL LUNG METASTASIS OF HUMAN FIBROSARCOMA CELLS

YIGSR, A SYNTHETIC LAMININ PEPTIDE, INHIBITS THE ENHANCEMENT BY CYCLOPHOSPHAMIDE OF EXPERIMENTAL LUNG METASTASIS OF HUMAN FIBROSARCOMA CELLS
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DOI:
10.1007/bf00132750
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发表时间:
1992-05-01
影响因子:
4
通讯作者:
SUGIOKA, Y
SUGIOKA, Y
中科院分区:
医学3区
文献类型:
--
作者:
IWAMOTO, Y;FUJITA, Y;SUGIOKA, Y

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肿瘤细胞必须附着在基底膜上,通过基底膜它们降解和迁移,以便扩散到远处。如果血管内皮细胞因抗癌药物预处理而受损,并且内皮下基底膜暴露,则恶性细胞与基底膜的附着以及随后在某些组织中的转移形成可能会增强。本研究分别用环磷酰胺(cyclophosphamide,CPA)预处理内皮细胞单层和小鼠,在体外能促进HT 1080人纤维肉瘤细胞与内皮细胞单层的粘附,在体内能促进HT 1080人纤维肉瘤细胞在肺内的定植。YIGSR是一种人工合成的层粘连蛋白五肽,当它与肿瘤细胞共同静脉注射时,可以抑制CPA对肺定植的增强作用。YIGSR的这种抑制作用可能是由于减少了HT 1080细胞对受损血管壁的粘附,因为YIGSR抑制了HT 1080细胞对CPA处理的内皮细胞单层的粘附和通过基底膜的侵袭。
Tumor cells must attach themselves to basement membranes, through which they degrade and migrate, in order to spread to distant sites. If vascular endothetial cells are damaged by pretreatment with anticancer drugs and the subendothelial basement membranes are exposed, the attachment of malignant cells to basement membranes and subsequent metastasis formation in some tissues may be enhanced. In this study, the pretreatment of endothelial cell monolayers and mice with cyclophosphamide (CPA) was respectively shown to promote the adhesion of HT1080 human fibrosarcoma cells to endothelial cell monolayers in vitro and lung colonization in vivo. YIGSR, a synthetic laminin pentapeptide, inhibited the enhancement of lung colonization by CPA when it was co-injected intravenously with tumor cells. This inhibitory effect of YIGSR may be due to a reduction in the adhesion of HT1080 cells to injured blood vessel walls since YIGSR inhibited both the adhesion of HT1080 cells to CPA-treated endothelial cell monolayers and the invasion through basement membranes in vitro.