SCM-chitin

SCM-Chitin (sulfated and carboxymethylated chitin) (Mw = 10000 to 60000) Inhibits cell attachment and migration of BI6-BL6 melanoma cells through extracellular matrix 64... 

F. Inhibition of Tumor Cell Arrest in Lungs by SCM-Chitin III... 

The effect of SCM-chitin III on tumor cell arrest was investigated to analyze the mechanism of tumor antimetastasis. Lung retention of I-labeled B16-BL6 cells was reduced more rapidly for 4-8 h after tumor inoculation by coinjection of SCM-chitin III than that of untreated mice (Fig. 7). A significant reduction of tumor cell arrest in the lungs was observed in heparin-injected mice. However, very little difference was detected between untreated mice and SCM-chitin-injected mice. 

Because SCM-chitin III showed a weak influence on tumor cell-induced platelet aggregation and on blood coagulation, these properties might stimulate the early phase of tumor cell arrest in blood vessels. Also, inhibition of tumor cell invasion into the basement membrane following endothelial cell retraction might be significant in the stabilization of tumor cell arrest at... 

To clarify the mechanism of inhibition of tumor cell invasion by SCM-chitin III, the influence of heparinoids on tumor cell migration through laminin and on the matrix-degrading enzymes (heparanase and type IV col-lagenase) was investigated in tumor cells in vitro. The inhibition of hapto-tactic migration of B16-BL6 cells through laminin-coated filters is shown in... 

Figure 7 Lung retention of [ l]IUdR-labeled tumor cells coinjected with chitin heparinoid into mice. [ IJIUdR-labeled B16-BL6 cells (3 X 10 ) were inoculated with PBS (o) 250 JLg SCM-chitin III ( ) CM-chitin (A) heparin (A) into C57BL/ 6 mice. The radio activity in the lungs was measured at various time intervals after the injection.

Figure 8 Dose-response of SCM-chitin III on haptotactic migration of tumor cells. B16-BL6 cells (2 X 10" ) were seeded on the filter precoated on the lower surface with 5 xg laminin. Various concentrations of SCM-chitin III were added into the lower compartment of a Transwell chamber. After a 6-h incubation, the migrant cells on the lower surface were visually counted. P > 0.001 compared with the control by Student s two-tailed r-test.

Fig. 8 in a SCM-chitin III concentration-dependent manner. CM-chitin showed no inhibitory effect at a concentration of 500 xg/mL. SCM-chitin III inhibited HS degradation by partially purified heparanase from B16-BL6 cells as did heparin in a concentration-dependent manner (Fig. 9), whereas CM-chitin had little influence at any of the indicated concentrations, except that of 1000 p.g/mL. On the other hand, degradation of H-labeled type IV collagen was inhibited over a 24-h period by more than 75% after treatment with 400 xg/mL of SCM-chitin III and approximately 20% inhibition after treatment with heparin. Little inhibition was shown by CM-chitin. A summary of the biological functions of SCM-chitin III and heparin are listed in Table 5. 

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