Kim W H, Schnaper H W, Nomizu M, Yamada Y, Kleinman H K
Laboratory of Developmental Biology, National Institute of Dental Research, NIH, Bethesda, Maryland 20892.
Cancer Res. 1994 Sep 15;54(18):5005-10.
The YIGSR (Tyr-Ile-Gly-Ser-Arg) peptide, derived from the laminin beta 1 chain, decreases tumor metastasis and growth in experimental animals. The mechanism responsible for this inhibition is not known. We now report that a 16-mer branched form of YIGSR, synthesized by the multimeric antigen peptide system, induced the apoptosis of HT-1080 cells in vitro at 30 micrograms/ml (approximately 3 microM). Tumor cells treated with this peptide showed the expected morphological changes associated with apoptosis, acridine orange staining of nuclei, increased numbers of 3'-OH ends of DNA in nuclei, a DNA ladder pattern on agarose gels, and increased transforming growth factor beta 1 mRNA by Northern blot. The specificity of this peptide was confirmed by inhibition of apoptosis with a neutralizing antibody to the peptide. In addition, the branched 16-mer peptides of scrambled sequence did not induce apoptosis. Our in vitro results suggest that apoptosis may play a role in the antimetastatic and antitumor effects associated with the YIGSR peptide.
源自层粘连蛋白β1链的YIGSR（酪氨酸-异亮氨酸-甘氨酸-丝氨酸-精氨酸）肽可减少实验动物的肿瘤转移和生长。导致这种抑制作用的机制尚不清楚。我们现在报告，通过多聚体抗原肽系统合成的一种16聚体分支形式的YIGSR，在体外以30微克/毫升（约3微摩尔）的浓度诱导HT-1080细胞凋亡。用该肽处理的肿瘤细胞表现出与凋亡相关的预期形态变化、细胞核的吖啶橙染色、细胞核中DNA 3'-OH末端数量增加、琼脂糖凝胶上的DNA梯状图谱以及通过Northern印迹法检测到的转化生长因子β1 mRNA增加。用该肽的中和抗体抑制凋亡证实了该肽的特异性。此外，序列混乱的分支16聚体肽不诱导凋亡。我们的体外研究结果表明，凋亡可能在与YIGSR肽相关的抗转移和抗肿瘤作用中发挥作用。
