title: Inhibition by sulfated chitin derivatives of invasion through extracellular matrix and enzymatic degradation by metastatic melanoma cells.
abstract: We have investigated the effects of sulfated chitin derivatives and heparin on the invasion of B16-BL6 melanoma cells through reconstituted basement membrane Matrigel which contains laminin, type IV collagen, heparin sulfate proteoglycan, and entactin. 6-O-sulfated chitin (S-chitin) and 6-O-sulfated and carboxymethyl chitin (SCM-chitin) significantly inhibited the penetration of tumor cells through Matrigel in parallel with the increased degree of sulfation. However, 6-O- and N-sulfated but partially N-deacetylated chitin derivative (SCM-chitosan) and CM-chitin had no effect. SCM-chitin with a high degree of sulfation (SCM-chitin III), which exhibited fairly low levels of anticoagulant activity, was more effective than intact heparin. SCM-chitin III and heparin were also shown to block the attachment and migration of tumor cells to laminin-coated substrates, which are considered to be involved in tumor invasion. The inhibition of cell attachment and migration by SCM-chitin III and heparin is likely to depend upon their specific binding to laminin molecules (possibly the heparin-binding domain). Degradation of heparan sulfate by heparanase was inhibited by SCM-chitin III and heparin in a dose-dependent manner. Surprisingly, SCM-chitin III could inhibit type IV collagenolytic activity of tumor cells more potently than heparin. Thus, nontoxic SCM-chitin III of low anticoagulant properties may provide a promising basis for the prevention of cancer metastasis.
authors.affiliation: Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Saiki
authors.forename: J
authors.initials: J
authors.lastname: Murata
authors.forename: M
authors.initials: M
authors.lastname: Nakajima
authors.forename: S
authors.initials: S
authors.lastname: Tokura
authors.forename: I
authors.initials: I
authors.lastname: Azuma
mesh_terms: D001667:Binding, Competitive; D002448:Cell Adhesion / Q000187:drug effects; D002686:Chitin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003470:Culture Media; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D013464:Sulfuric Acids / Q000494:pharmacology
chemical_list: D003470:Culture Media; D007797:Laminin; D013464:Sulfuric Acids; D002686:Chitin; C044872:O-(carboxymethyl)chitin; D006493:Heparin