Identification of a synthetic nonapeptide sequence that inhibits motility in culture of a melanoma subclone that possesses a high metastatic potential.
A synthetic nonapeptide fragment of thrombin inhibits the cellular motility in culture of a human melanoma subclone that possesses a high metastatic potential in mice. Concomitant with the loss of ability to translocate in culture, these cells exhibit increases in the average length of actin cables and cellular surface area in contact with the substratum. The spreading activity is observed at a nonapeptide concentration of 1 nM within 1 hr of exposure at 37 degrees C. Pretreatment of cells with this nonapeptide does not block signal transduction through plasma membrane receptors for the following growth or differentiation factors: alpha-melanotropin (alpha-melanocyte-stimulating hormone), nerve growth factor, and transforming growth factor type beta. Results of the present study suggest an approach to cancer chemotherapy in which naturally occurring peptides from two functionally orthogonal classes may be used to perform two complementary functions: inhibition of metastasis and induction of differentiation.
D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003599:Cytoskeleton / Q000648:ultrastructure; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000473:pathology*; D009362:Neoplasm Metastasis; D009414:Nerve Growth Factors / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D013917:Thrombin; D015291:Transforming Growth Factors; D014407:Tumor Cells, Cultured / Q000473:pathology; D014764:Viral Proteins
D009414:Nerve Growth Factors; D009842:Oligopeptides; D010455:Peptides; D014764:Viral Proteins; D015291:Transforming Growth Factors; D009074:Melanocyte-Stimulating Hormones; D013917:Thrombin