Identification of a synthetic nonapeptide sequence that inhibits motility in culture of a melanoma subclone that possesses a high metastatic potential.

Abstract

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 370C. Pretreatment of cells with this nonapeptide does not block signal transduction through plasma membrane receptors for the following growth or differentiation factors: a-melanotropin (a-melanocyte-stimulating hormone), nerve growth factor, and transforming growth factor type (3. 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.

Integrin Expression in Malignant Melanoma and Their Role in Cell Attachment and Migration on Extracellular Matrix Proteins

“…Purification of proteolytic fragments of FN, CN, and LN have identified multiple, distinct domains promoting or inhibiting cell attachment or cell migration (21)(22)(23). Synthetic peptides made from small regions of the proteolytic fragments have identified specific peptides which modulate cell migration and metastasis of murine melanoma cells (21,(24)(25)(26)(27)(28)(29). Recently, peptide inhibitors and mAb studies on human melanoma cells have been reported to inhibit motility (34).…”