Inhibitory Effect of Chitin Heparinoids on the Lung Metastasis of B16‐BL6 Melanoma

Structure‐function studies for the antimetastatic activity of chemically modified chitin heparinoids composed of N‐acetyl glucosamine units were performed in an experimental lung metastasis model. 6‐O‐Sulfatcd chitin (S‐chitin) significantly inhibited the lung tumor colonization in proportion to the degree of sulfation. However, 6‐O‐ and N‐sulfated but partially N‐deacetylated chitin (S‐chitosan), and 6‐O‐carboxymethylated chitin (CM‐chitin) had no effect. 6‐O‐Sulfated CM‐chitin (SCM‐chitin), which exhibited fairly low levels of anticoagulant activity, was also more effective than intact heparin. Furthermore, SCM‐chitin with a high degree of sulfation (SCM‐chitin III) caused a marked decrease of the number of lung tumor colonies in the spontaneous lung metastasis model. These results strongly suggest that 6‐O‐sulfate and N‐acetyl groups in the glucosamine unit were required for the antimetastatic effect of chitin heparinoids as well as heparin, and SCM‐chitin III may be of therapeutic benefit for the prevention of tumor metastasis.