Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors.
Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors.
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DOI：
10.1186/1476-4598-9-138
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发表时间：
2010-06-04
期刊：
影响因子：
37.3
通讯作者：
Cohn SL
中科院分区：
文献类型：
--
作者：
Chlenski A;Guerrero LJ;Peddinti R;Spitz JA;Leonhardt PT;Yang Q;Tian Y;Salwen HR;Cohn SL
需要新的，更有效的策略来治疗高度侵袭性的神经母细胞瘤。我们的实验室先前已经表明，全长分泌蛋白酸性和富含半胱氨酸（α）和β肽对应于蛋白质的卵泡抑素结构域（FS-E）有效地阻断血管生成，并抑制临床前模型中神经母细胞瘤肿瘤的生长。肽FS-E结构复杂且难以生产，限制了其作为临床治疗剂的潜力。在这项研究中，我们合成了两个更小，结构更简单的肽，FSEN和FSEC，分别对应于N-和C-末端环的肽FS-E。我们表明，肽FSEN和FSEC在体外和体内具有抗血管生成活性，虽然FSEC更有效。肽FSEC还显著抑制神经母细胞瘤异种移植物的生长。组织学检查表明，在对照神经母细胞瘤异种移植瘤中，肿瘤血管生成具有结构异常、迂曲的血管特征。相比之下，在肿瘤中观察到的血管，用β肽处理，是薄壁的，结构上更正常。使用一种新的方法来定量评估血管异常，我们证明了这两种肽都诱导了血管结构的变化，这与血管正常化是一致的。我们的研究结果表明，FSEC肽在神经母细胞瘤中具有有效的抗血管生成和抗肿瘤发生作用。其简单的结构和易于生产表明，它可能在治疗高风险的神经母细胞瘤和其他类型的儿童和成人癌症，这取决于血管生成的临床效用。
New, more effective strategies are needed to treat highly aggressive neuroblastoma. Our laboratory has previously shown that full-length Secreted Protein Acidic and Rich in Cysteine (SPARC) and a SPARC peptide corresponding to the follistatin domain of the protein (FS-E) potently block angiogenesis and inhibit the growth of neuroblastoma tumors in preclinical models. Peptide FS-E is structurally complex and difficult to produce, limiting its potential as a therapeutic in the clinic. In this study, we synthesized two smaller and structurally more simple SPARC peptides, FSEN and FSEC, that respectively correspond to the N-and C-terminal loops of peptide FS-E. We show that both peptides FSEN and FSEC have anti-angiogenic activity in vitro and in vivo, although FSEC is more potent. Peptide FSEC also significantly inhibited the growth of neuroblastoma xenografts. Histologic examination demonstrated characteristic features of tumor angiogenesis with structurally abnormal, tortuous blood vessels in control neuroblastoma xenografts. In contrast, the blood vessels observed in tumors, treated with SPARC peptides, were thin walled and structurally more normal. Using a novel method to quantitatively assess blood vessel abnormality we demonstrated that both SPARC peptides induced changes in blood vessel architecture that are consistent with blood vessel normalization. Our results demonstrate that SPARC peptide FSEC has potent anti-angiogenic and anti-tumorigenic effects in neuroblastoma. Its simple structure and ease of production indicate that it may have clinical utility in the treatment of high-risk neuroblastoma and other types of pediatric and adult cancers, which depend on angiogenesis.
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影响因子：
11.4
作者：
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通讯作者：
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作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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