Nomizu M, Yamamura K, Kleinman H K, Yamada Y
Laboratory of Developmental Biology, National Institute of Dental Research, NIH, Bethesda, Maryland 20892.
Cancer Res. 1993 Aug 1;53(15):3459-61.
The Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide derived from the laminin B1 chain has been shown to decrease tumor growth and metastasis. Utilizing the multimeric antigen peptide system assembled on a branched lysine core, we synthesized several sizes of multimeric YIGSR, (CH3CO-Tyr-Ile-Gly-Ser-Arg-Gly)16-Lys8-Lys4-Lys2 -Lys-Gly [(Ac-YIGSRG)16 K8K4K2KG] (designated Ac-Y16), (Ac-YIGSRG)8K4K2KG (Ac-Y8), and (Ac-YIGSRG)4K2KG (Ac-Y4), and related peptides, Ac-(YIGSRG)4-NH2 (Ac-Y4L) and Ac-YIGSR-NH2 (Ac-Y1) and evaluated their biological activities in inhibiting tumor growth and metastasis. Coinjection of 0.2 mg/mouse of Ac-Y16 i.v. with B16-F10 mouse melanoma cells inhibited lung colony formation by 97%, whereas 0.2 mg/mouse of Ac-Y1 inhibited by 50%. The larger the peptide (Ac-Y16 > Ac-Y8 > Ac-Y4 > Ac-Y1), the more inhibitory effect there was on lung metastasis. Ac-Y16 also inhibited the growth of s.c.-injected B16-F10 tumors. These data demonstrate that the multimeric YIGSR peptides strongly enhanced the activity of YIGSR in inhibiting tumor growth and metastasis and suggest that these compounds are potentially useful for clinical applications.
源自层粘连蛋白B1链的Tyr-Ile-Gly-Ser-Arg（YIGSR）肽已被证明可减少肿瘤生长和转移。利用组装在分支赖氨酸核心上的多聚体抗原肽系统，我们合成了几种不同大小的多聚体YIGSR，即（CH3CO-Tyr-Ile-Gly-Ser-Arg-Gly）16-Lys8-Lys4-Lys2-Lys-Gly [（Ac-YIGSRG）16 K8K4K2KG]（命名为Ac-Y16）、（Ac-YIGSRG）8K4K2KG（Ac-Y8）和（Ac-YIGSRG）4K2KG（Ac-Y4），以及相关肽Ac-（YIGSRG）4-NH2（Ac-Y4L）和Ac-YIGSR-NH2（Ac-Y1），并评估了它们在抑制肿瘤生长和转移方面的生物学活性。静脉注射0.2 mg/小鼠的Ac-Y16与B16-F10小鼠黑色素瘤细胞共同注射时，可抑制肺集落形成97%，而0.2 mg/小鼠的Ac-Y1抑制率为50%。肽越大（Ac-Y16 > Ac-Y8 > Ac-Y4 > Ac-Y1），对肺转移的抑制作用越强。Ac-Y16还抑制皮下注射的B16-F10肿瘤的生长。这些数据表明，多聚体YIGSR肽强烈增强了YIGSR抑制肿瘤生长和转移的活性，并表明这些化合物在临床应用中具有潜在用途。
