Apoptosis in human fibrosarcoma cells is induced by a multimeric synthetic Tyr-Ile-Gly-Ser-Arg (YIGSR)-containing polypeptide from laminin.
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.
Kim
W H
WH
Laboratory of Developmental Biology, National Institute of Dental Research, NIH, Bethesda, Maryland 20892.
Schnaper
H W
HW
Nomizu
M
M
Yamada
Y
Y
Kleinman
H K
HK
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007797:Laminin / Q000737:chemistry*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000032:analysis; D014407:Tumor Cells, Cultured
D007797:Laminin; D009842:Oligopeptides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine