Evidence that sulphated polysaccharides inhibit tumour metastasis by blocking tumour‐cell‐derived heparanases
Evidence that sulphated polysaccharides inhibit tumour metastasis by blocking tumour‐cell‐derived heparanases
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硫酸多糖通过阻断肿瘤细胞衍生的乙酰肝素酶来抑制肿瘤转移的证据
DOI：
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发表时间：
1987
影响因子：
6.4
通讯作者：
P. Underwood
中科院分区：
文献类型：
--
作者：
C. Parish;D. R. Coombe;K. Jakobsen;F. A. Bennett;P. Underwood
本实验室最近的研究表明，几种硫酸多糖可以抑制大鼠乳腺癌13762 MAT的转移，可能是通过阻止肿瘤细胞通过血管壁。为了直接测试这种可能性，将13762 MAT细胞与（35 S）O 4 =-标记的内皮下细胞外基质（ECM）一起培养，并在存在或不存在不同硫酸化多糖的情况下监测ECM降解。通过十二烷基硫酸钠聚丙烯酰胺凝胶电泳和随后的放射自显影检测降解产物。先前已显示具有抗转移活性的5种硫酸化多糖是13762 MAT细胞降解内皮下ECM的有效抑制剂。相比之下，在测试的4种未能抑制转移的多糖中，3种对ECM分解没有影响，一种（角叉菜胶-κ）在抑制ECM降解方面比抗转移制剂有效性低得多。研究还表明，13762 MAT细胞产生硫酸乙酰肝素特异性糖苷酶（乙酰肝素酶），其降解ECM的硫酸乙酰肝素侧链，这种酶的作用而不是其他ECM溶解酶的作用受到抗转移硫酸多糖的抑制。其他实验表明，多糖的抗凝活性可能在其抗转移作用中起次要作用，因为肝素通过抗凝血酶III柱几乎完全耗尽（98-99.5%）具有抗凝活性的肝素分子，保留其抑制13762 MAT肝素酶的能力，并且在抑制肿瘤细胞转移方面几乎与普通肝素一样有效。总的来说，这些数据表明硫酸多糖通过抑制肿瘤细胞源性肝素酶来抑制13762 MAT细胞的转移，所述肝素酶参与肿瘤细胞穿透血管内皮及其下面的基底膜。
Recent studies in this laboratory demonstrated that several sulphated polysaccharides can inhibit metastasis of the rat mammary adenocarcinoma 13762 MAT, probably by preventing the passage of tumour cells through the walls of blood vessels. In order to directly test this possibility, 13762 MAT cells were cultured with (35S)O4=‐labelled subendothelial extracellular matrices (ECM) and ECM degradation was monitored in either the presence or absence of different sulphated polysaccharides. Degradation products were detected by sodium dodecyl sulphate polyacrylamide gel electrophoresis and subsequent autoradiography. The 5 sulphated polysaccharides that had previously been shown to possess anti‐metastatic activity were potent inhibitors of the degradation of subendothelial ECM by 13762 MAT cells. In contrast, of the 4 polysaccharides tested that failed to inhibit metastasis, 3 had no effect on ECM breakdown and one (carrageenan‐kappa) was substantially less effective at inhibiting ECM degradation than the anti‐metastatic preparations. It was also shown that 13762 MAT cells produce a heparan sulphate‐specific glycosidase (heparanase) that degrades the heparan sulphate side‐chains of the ECM, the action of this enzyme rather than that of other ECM‐solubilizing enzymes being inhibited by the anti‐metastatic sulphated polysaccharides. Additional experiments indicated that the anti‐coagulant activity of the polysaccharides probably plays a minor role In their anti‐metastatic effects since heparin, almost completely depleted (98–99.5%) of heparin molecules with anti‐coagulant activity by passage over an anti‐thrombin III column, retained its ability to inhibit 13762 MAT heparanases and was almost as effective as unfractionated heparin at inhibiting tumour‐cell metastasis. Collectively, these data suggest that sulphated polysaccharides inhibit the metastasis of 13762 MAT cells by inhibiting tumour‐cell‐derived heparanases involved in the penetration of the vascular endothelium and Its underlying basement membrane by tumour cells.
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DOI：
10.1016/s0021-9258(17)43350-3
发表时间：
1984-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. Nakajima;T. Irimura;N. Ferrante;G. Nicolson
通讯作者：
M. Nakajima;T. Irimura;N. Ferrante;G. Nicolson
DOI：
10.1172/jci112104
发表时间：
1985-10
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Y. Matzner;M. Bar‐Ner;J. Yahalom;R. Ishai‐Michaeli;Z. Fuks;I. Vlodavsky
通讯作者：
Y. Matzner;M. Bar‐Ner;J. Yahalom;R. Ishai‐Michaeli;Z. Fuks;I. Vlodavsky
影响因子：
3.4
作者：
Pu，Huangsheng;Gao，Peng;Lu，Hongbing
通讯作者：
Lu，Hongbing
影响因子：
2.9
作者：
IRIMURA, T;NAKAJIMA, M;NICOLSON, GL
通讯作者：
NICOLSON, GL
影响因子：
2.9
作者：
NAKAJIMA, M;IRIMURA, T;NICOLSON, GL
通讯作者：
NICOLSON, GL