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Sulphated polysaccharides with antimetastatic activity act by inhibiting tumour cell secreted endoglycosidases
Cell Biology
International
Reports,
Vol. 11, No. 3, March
253
1987
"Sulphated polysaccharides with antimetastatic activity act by inhibiting tumour cell secreted endoglycosidases". D.R. Coombe, C.R. Parish, K.B. Jakobsen and P.A. Underwood*. John Curtin School of Medical Research, Dept. of Microbiology, Australian National University, Canberra, Australia; * C.S.I.R.O. Division of Molecular Biology, North Hyde, Sydney, Australia. A variety of sulphated polysaccharides were found to significantly inhibit lung metastases resulting from the intravenous injection of cells from the rat mammary adenocarcinoma 13762 MAT. The most antimetastatic polysaccharides were heparin, fucoidan and carrageenan lambda. Anticoagulation, the usual explanation for such findings, was found not to be a sufficient explanation for the antimetastatic effect of at least one of these polysaccharides. Since, heparin, a very potent antimetastatic agent, when depleted of its anticoagulant activity by chromatography on antithrombin III, retained its capacity to dramatically inhibit metastases. It is proposed that particular sulphated polysaccharides inhibit metastasis by interfer ing with the breakdown by tumour cell secreted enzymes of the extracellular matrix of vascular endothelia. 13762 MAT cells were found to secrete enzymes that degrade the extracellular matrix of endothelial cells. At least some of these enzymes were heparanases. All of the polysacrhariden
that
inhi~hiterl
metastasis
were
;11sn
inhibitors
the 13762 MAT cell secreted endoglycosidases and conversely all the polysaccharides that failed to inhibit metastasis had much less (or no detectable) endoglycosidase inhibitory activity. Moreover, both anticoagulant depleted and anticoagulant enriched heparin fractions exhibited a similar ability to inhibit the endoglycosidases. Subtle differences in the potency of the antimetastatic polysaccharides, however, cannot be explained by differences in their endoglycosidase inhibitory activity. It is proposed that the ability of the polysaccharides to bind and localise on the endothelial cells is a contributing factor to their antimetastatic activity.
nf
International
Reports,
Vol. 11, No. 3, March
253
1987
"Sulphated polysaccharides with antimetastatic activity act by inhibiting tumour cell secreted endoglycosidases". D.R. Coombe, C.R. Parish, K.B. Jakobsen and P.A. Underwood*. John Curtin School of Medical Research, Dept. of Microbiology, Australian National University, Canberra, Australia; * C.S.I.R.O. Division of Molecular Biology, North Hyde, Sydney, Australia. A variety of sulphated polysaccharides were found to significantly inhibit lung metastases resulting from the intravenous injection of cells from the rat mammary adenocarcinoma 13762 MAT. The most antimetastatic polysaccharides were heparin, fucoidan and carrageenan lambda. Anticoagulation, the usual explanation for such findings, was found not to be a sufficient explanation for the antimetastatic effect of at least one of these polysaccharides. Since, heparin, a very potent antimetastatic agent, when depleted of its anticoagulant activity by chromatography on antithrombin III, retained its capacity to dramatically inhibit metastases. It is proposed that particular sulphated polysaccharides inhibit metastasis by interfer ing with the breakdown by tumour cell secreted enzymes of the extracellular matrix of vascular endothelia. 13762 MAT cells were found to secrete enzymes that degrade the extracellular matrix of endothelial cells. At least some of these enzymes were heparanases. All of the polysacrhariden
that
inhi~hiterl
metastasis
were
;11sn
inhibitors
the 13762 MAT cell secreted endoglycosidases and conversely all the polysaccharides that failed to inhibit metastasis had much less (or no detectable) endoglycosidase inhibitory activity. Moreover, both anticoagulant depleted and anticoagulant enriched heparin fractions exhibited a similar ability to inhibit the endoglycosidases. Subtle differences in the potency of the antimetastatic polysaccharides, however, cannot be explained by differences in their endoglycosidase inhibitory activity. It is proposed that the ability of the polysaccharides to bind and localise on the endothelial cells is a contributing factor to their antimetastatic activity.
nf