The adhesive interaction between
tumor cells, host cells or extracellular matrix (ECM) plays a crucial role in metastatic formation. We used synthetic
polypeptide containing a repetitive core sequence,
Arg-Gly-Asp (RGD), of cell-adhesive molecules;
poly (RGD), to antagonize the adhesive interaction between ECM and
integrin receptors on
tumor cell surface during the metastatic cascade.
Poly (RGD) significantly inhibited the experimental lung and liver
metastasis as compared with
RGD peptide when it was coinjected i.v. with different types of
tumors. In a spontaneous lung
metastasis model using B16-BL6
melanoma, multiple i.v. administrations of
poly (RGD), before or after surgical excision of the primary
tumor, resulted in significant reduction of the lung colonization. The mechanism responsible for the inhibition is partly associated with the ability to interfere with cell functions such as adhesiveness, motility, and invasiveness in the metastatic process.
Poly (RGD) showed no cytotoxicity against host and
tumor cells. Thus, the regulation of adhesive interaction of
tumor cells with ECM or host cells by anti-adhesive
polypeptides may provide a promising approach for the prevention of
tumor metastasis.