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-Sulfated 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 anti-metastatic effect of chitin heparinoids as well as heparin, and SCM-chitin III may be of therapeutic benefit for the prevention of tumor metastasis.
Murata
J
J
Institute of Immunological Science, Hokkaido University, Sapporo.
Saiki
I
I
Nishimura
S
S
Nishi
N
N
Tokura
S
S
Azuma
I
I
D000818:Animals; D000970:Antineoplastic Agents; D002460:Cell Line; D002686:Chitin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008545:Melanoma / Q000188:drug therapy / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002686:Chitin; D006493:Heparin