Naturally produced extracellular matrix inhibits growth rate and invasiveness of human osteosarcoma cancer cells
Naturally produced extracellular matrix inhibits growth rate and invasiveness of human osteosarcoma cancer cells
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DOI：
10.1007/bf02698042
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发表时间：
2007-01-01
期刊：
影响因子：
3.4
通讯作者：
Rath, M.
中科院分区：
文献类型：
--
作者：
Ivanov, V.;Ivanova, S.;Rath, M.
某些天然存在的营养素和维生素的增强补充与人类癌症的发生和进展的减少有关。这种作用的确切机制仍在调查中。细胞外基质（ECM）在肿瘤的发生发展中起着关键作用。因此，我们研究了营养素是否可以通过改变ECM的生物学特性来发挥抗癌作用。正常人皮肤成纤维细胞的汇合培养物在测试化合物存在下在7天温育期期间允许产生和存款ECM。随后，去除成纤维细胞，并在普通细胞生长培养基中测定预先形成的ECM上的人骨肉瘤细胞（细胞系U2-OS、MMNG或SK. ES 1）的新鲜放置培养物的生长速率。此外，ECM由成纤维细胞沉积在多孔塑料膜的上表面上，并在非补充培养基中测定骨肉瘤细胞随后向另一侧的迁移。结果表明，与未补充的对照相比，用抗坏血酸、赖氨酸、脯氨酸、精氨酸、半胱氨酸和绿色茶多酚的混合物处理的正常成纤维细胞产生的ECM显著降低骨肉瘤细胞的生长速率和侵袭活性。ECM性质的变化伴随着ECM蛋白和糖胺聚糖组成的免疫化学测定的显着变化。我们的结论是，营养素的抗癌作用涉及ECM生物学特性的有益变化。ECM成分在ECM依赖性调节肿瘤细胞活性的作用进行了讨论。
Enhanced supplementation with certain naturally occurring nutrients and vitamins has been associated with a reduction in occurrence and progression of human cancer. The exact mechanisms of this action are still under investigation. Extracellular matrix (ECM) plays a key role in the development of cancer. Therefore, we studied whether nutrients could exert anticancer effects through alteration of ECM biological properties. Confluent cultures of normal human dermal fibroblasts were allowed to produce and deposit ECM during a 7 d incubation period in the presence of tested compounds. Subsequently, fibroblasts were removed and the growth rates of freshly placed cultures of human osteosarcoma cells (lines U2-OS, MMNG, or SK.ES1) on pre-formed ECM were assayed in plain cell growth medium. In addition, ECM was deposited by fibroblasts on the upper surface of a porous plastic membrane and the subsequent migration of osteosarcoma cells to the other side was assayed in non-supplemented medium. The results demonstrated that the ECM produced by normal fibroblasts treated with a mixture of ascorbic acid, lysine, proline, arginine, cysteine, and green tea polyphenols significantly reduced the growth rate and invasive activity of osteosarcoma cells in contrast to the non-supplemented control. The changes in ECM properties were accompanied by significant changes in ECM protein and glycosaminoglycan composition as assayed immunochemically. We conclude that anticancer effects of nutrients involve beneficial changes in ECM biological properties. The role of ECM components in ECM-dependent regulation of tumor cell activities is discussed.