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层粘连蛋白序列Tyr-Ile-Gly-Ser-Arg（YIGSR）的多聚体形式对人纤维肉瘤细胞HT1080血管生成、肿瘤生长及实验性转移的抑制作用

Inhibition of angiogenesis, tumour growth and experimental metastasis of human fibrosarcoma cells HT1080 by a multimeric form of the laminin sequence Tyr-Ile-Gly-Ser-Arg (YIGSR).

作者信息

Iwamoto Y, Nomizu M, Yamada Y, Ito Y, Tanaka K, Sugioka Y

机构信息

Department of Orthopaedic Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

出版信息

Br J Cancer. 1996 Mar;73(5):589-95. doi: 10.1038/bjc.1996.102.

DOI:10.1038/bjc.1996.102
PMID:8605091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2074333/
Abstract

A multimeric peptide, Ac-Y16, consisting of 16 YIGSR sequences from laminin was evaluated for its effect on experimental metastasis, angiogenesis and tumour growth of HT1080 human fibrosarcoma cells. Co-injection of 0.5 mg per mouse of Ac-Y16 i.v. with HT 1080 cells inhibited lung colonisation by 100%, whereas 0.5 mg per mouse of monomeric Ac-YIGSR-NH2(AcY1) inhibited by 94%. Ac-Y16 did not show any direct cytotoxicity in tumour cells in vivo. The effect of the peptides on angiogenesis and tumour growth respectively were evaluated by counting areas of neovessels and weighing tumours after the s.c. implantation of HT1080 cells with basement membrane extracts and the peptide into nude mice. Co-injection of 0.5 mg per mouse of AC-Y16 s.c. with HT1080 cells inhibited angiogenesis and tumour growth by 92% (P<0.05) and 76% (P<0.05) respectively, whereas 0.5 mg per mouse of monomeric Ac-YIGSR-NH2(Ac-Y1) inhibited angiogenesis and tumour growth by 40% (P<0.05) and 9% (P>0.05) respectively. It can be inferred from these data that anti-tumour effects of Ac-Y16 are likely to result from anti-angiogenesis. Intraperitoneal administration of Ac-Y16 was also effective in inhibiting angiogenesis, tumour growth and lung colonisation of HT1080 cells. It was concluded that the multimeric YIGSR-containing peptide, Ac-Y16, inhibits angiogenesis, tumour growth and experimental metastasis more than the monomeric form and that it is active when administered i.p., iv. and s.c.

摘要

对一种由层粘连蛋白的16个YIGSR序列组成的多聚体肽Ac-Y16进行了评估，以研究其对HT1080人纤维肉瘤细胞的实验性转移、血管生成和肿瘤生长的影响。每只小鼠静脉注射0.5 mg Ac-Y16与HT 1080细胞共同注射时，肺转移定殖抑制率达100%，而每只小鼠注射0.5 mg单体Ac-YIGSR-NH2（AcY1）时，抑制率为94%。Ac-Y16在体内对肿瘤细胞未显示出任何直接细胞毒性。在用基底膜提取物和该肽将HT1080细胞皮下植入裸鼠后通过计数新生血管面积和称量肿瘤重量分别评估了这些肽对血管生成和肿瘤生长的影响。每只小鼠皮下注射0.5 mg AC-Y16与HT1080细胞共同注射时，血管生成和肿瘤生长的抑制率分别为92%（P<0.05）和76%（P<0.05）；而每只小鼠注射0.5 mg单体Ac-YIGSR-NH2（Ac-Y1）时血管生成和肿瘤生长抑制率分别为40%（P<0.05）和9%（P>0.05）。从这些数据可以推断，Ac-Y16的抗肿瘤作用可能源于抗血管生成。腹腔注射Ac-Y16对抑制HT1080细胞血管生成、肿瘤生长和肺转移定殖也有效。得出的结论是，含YIGSR的多聚体肽Ac-Y16比单体形式更能抑制血管生成、肿瘤生长和实验性转移，并且腹腔注射、静脉注射和皮下注射时均具有活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f370/2074333/b7ef3d66e2bf/brjcancer00033-0040-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f370/2074333/b7ef3d66e2bf/brjcancer00033-0040-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f370/2074333/b7ef3d66e2bf/brjcancer00033-0040-a.jpg

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