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首页> 美国卫生研究院文献>Neuro-Oncology >P52TARGETING COLLAGEN REGULATION IN GLIOBLASTOMA MULTIFORME
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P52TARGETING COLLAGEN REGULATION IN GLIOBLASTOMA MULTIFORME

机译：胶质母细胞瘤中P52靶向胶原蛋白的调控

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INTRODUCTION: Extracellular matrices (ECM) are quintessential complex structures that provide cells and tissues with functional support for adhesion, migration, cell-to-cell communication and differentiation. Collagens are fibrillar proteins that constitute the major component of ECM and have a key structural role. Intracellular maturation of collagen precursors, prior to secretion, is dependent on the hydroxylation of the collagen proline residues which is mediated by the prolyl 4-hydroxylases (P4H) family of enzymes. Although, ECM and collagen prolyl-hydroxylases have been shown to be important players in cancer migration and invasion, little is known of their role in brain tumours. METHOD: To examine the role of P4H enzymes in the biology of GBM we profiled their expression in a panel of GBM cell lines a variety of techniques including RT-PCR, western blotting and MSP. For functional studies we assesed the effects of two independent inhibitors of P4H on the growth of these lines using proliferation and apoptotic assays (SRB and Annexin V respectively). RESULTS: Pharmacological inhibition of collagen prolyl-hydroxylases dramatically reduced the proliferation of a panel of GBM cell lines. This reduction was independent of apoptosis. CONCLUSION: Our preliminary results show that collagen biosynthesis plays an important role in the growth of GBM and therefore could be a potential therapeutic strategy that needs further investigation.
机译：简介：细胞外基质（ECM）是典型的复杂结构，可为细胞和组织提供粘附，迁移，细胞间通讯和分化的功能支持。胶原蛋白是构成ECM主要成分的纤维蛋白，并具有关键的结构作用。在分泌之前，胶原前体的细胞内成熟取决于胶原脯氨酸残基的羟基化，其由脯氨酰4-羟化酶（P4H）家族的酶介导。尽管已经证明ECM和胶原脯氨酰羟化酶在癌症迁移和侵袭中起重要作用，但人们对其在脑肿瘤中的作用知之甚少。方法：为了检查P4H酶在GBM生物学中的作用，我们通过多种技术（包括RT-PCR，western blotting和MSP）分析了它们在GBM细胞系中的表达。对于功能研究，我们使用增殖和凋亡分析（分别为SRB和Annexin V）评估了两种独立的P4H抑制剂对这些品系生长的影响。结果：胶原蛋白脯氨酰羟化酶的药理抑制作用显着降低了一组GBM细胞系的增殖。这种减少与细胞凋亡无关。结论：我们的初步结果表明，胶原蛋白的生物合成在GBM的生长中起着重要的作用，因此可能是潜在的治疗策略，需要进一步研究。

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