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首页> 外文期刊>Journal of Cellular Physiology >Specific degradation of subendothelial matrix proteoglycans by brain-metastatic melanoma and brain endothelial cell heparanases.
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Specific degradation of subendothelial matrix proteoglycans by brain-metastatic melanoma and brain endothelial cell heparanases.

机译:特定的皮下基质降解由brain-metastatic黑色素瘤和蛋白聚糖大脑内皮细胞heparanases。

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One of the many features of the malignant phenotype, in vitro and in vivo, is elevated heparanase production and activity. Using in vitro model systems, we examined the capacity of murine (B16B15b) and human (70W) brain-metastatic melanoma cells to degrade the subendothelial matrix produced by endothelial cell monolayer cultures. B16B15b and 70W melanoma cells solubilized sulfated matrix proteoglycans at levels significantly higher than their parental lines (B16F1, MeWo). Sulfated matrix proteoglycans were rich in heparan sulfate (HSPGs), with minor amounts of chondroitin and dermatan sulfates. When matrix HSPGs were treated with pronase and alkaline borohydride to cleave the core proteins, the resulting glycosaminoglycan chains (GAGs) had an estimated M(r) of approximately 2.7 x 10(4) Da, with a minor subpopulation possessing an M(r) of approximately 4.5 x 10(4) Da. After their incubation with brain-metastatic melanoma cells, new HS fragments with lower M(r) estimated at approximately 9 x 10(3) Da were detected. This confirms action in these cells of heparanase, which is capable of cleaving GAGs at specific intrachain sites and releasing fragments of a relatively high M(r). The pattern of HSPG degradation by brain-metastatic melanoma cells differed from that of less metastatic parental cells or cells metastatic to organs other than the brain. Moreover, supraadditive levels of heparanase activity were found when brain endothelial cells were coin-cubated with brain-metastatic melanoma cells in equicellular amounts. Cooperative interactions between heparanases from tumor and endothelial sources in the invasion process are suggested and their potential mechanisms discussed.
机译:恶性的许多特性之一表型,在体外和体内,是升高的heparanase生产和活动。体外模型系统,我们检查的能力小鼠(B16B15b)和人类brain-metastatic (70 w)黑色素瘤细胞降低皮下矩阵由内皮细胞单层文化。可溶性蛋白聚糖硫酸矩阵水平明显高于他们的父母行(B16F1 MeWo)。富含硫酸乙酰肝素蛋白聚糖(HSPGs),少量的软骨素和dermatan硫酸盐。硼氢化与链霉蛋白酶和碱性裂开核心蛋白,由此产生粘多糖链(笑话)估计M (r)的大约2.7 x 10(4)哒,,小族群拥有一个M (r)大约4.5 x 10(4)哒。孵化与brain-metastatic黑色素瘤细胞,新商品片段M (r)较低的估计大约9 x 10(3)达被检测到。确认行动heparanase这些细胞,在特定的能力裂开的笑话吗链内的网站和释放的碎片相对较高的M (r)。降解brain-metastatic黑色素瘤细胞不同于低转移性的父母细胞或细胞转移以外的器官大脑。heparanase活动被发现,当大脑内皮细胞是coin-cubated在equicellular brain-metastatic黑色素瘤细胞金额。heparanases肿瘤和内皮来源入侵过程建议和他们潜在的机制进行了讨论。

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