We have investigated the effect of sulfated
chitin derivatives on the intravascular events in the metastatic cascade.
6-O-Sulfated carboxymethyl chitin (
SCM-chitin III), as well as
heparin, significantly inhibited the arrest of B16-BL6 cells in lungs after co-injection with radiolabeled
tumor cells, but carboxymethylated
chitin (
CM-chitin) had no effect.
Heparin showed a potent inhibitory effect on
tumor cell-elicited platelet aggregation and on blood coagulation, which can subsequently enhance the survival, arrest and invasiveness of
tumor cells, whereas
SCM-chitin III showed much weaker properties. In contrast,
SCM-chitin III was found to inhibit the adhesion of
tumor cells to subendothelial matrix, while
heparin did not.
SCM-chitin III was still active in inhibiting experimental lung
metastasis even in mice which had been pretreated with anti-
asialo GM1 serum or
carrageenan to eliminate NK cells or macrophages. Thus, these results suggest that
SCM-chitin-mediated inhibition of
tumor metastases is distinct from that by
heparin and may be due to interference with
tumor cell arrest in the capillaries and consequently to the inhibition of
tumor cell adhesion to subendothelial matrix.