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Nature:能抑制肿瘤扩散新蛋白maspin

劳森健康研究所的约翰·刘易斯、安·钱伯斯及同事在《实验室研究》杂志上发表了其研究成果:一种名为maspin的蛋白质能抑制如乳房癌、卵巢癌、头颈癌等癌细胞的形成、增长和扩散,但仅限于它在细胞核内。

为了评估maspin蛋白在肿瘤生长和发展方面的作用,研究人员选择了两种癌症进行测试:高侵略性的头颈癌和会扩散至淋巴结和肺部的乳腺癌。该小组将一个maspin蛋白注入癌细胞的细胞核,另一个被阻绝在细胞核之外,随后分别注入患癌症的鸡胚和小鼠模型中。

实验结果显示,当maspin蛋白注入到癌细胞的内核时,其基本扩散能力明显降低,新陈代谢的发生率从75%降至40%;而maspin蛋白在细胞核外时则使癌细胞更易扩散。这些发现表明,maspin蛋白在细胞中的位置显然影响到了癌细胞的行为,从而最终决定了癌症的扩散性以及治疗效果。但由于maspin蛋白在细胞中所处位置不同可能会导致正反两种结果,目前将这一信息用于预测癌症患者的进展有点困难。

研究人员表示,新陈代谢占到了癌症死亡原因的90%,而细胞核中的maspin蛋白显著减少了癌症远端转移的范围和大小。这个研究可能帮助医生更好地了解癌症的扩散性,为药物开发提供新的靶点。

maspin蛋白质能抑制癌细胞扩散

maspin蛋白质能抑制癌细胞扩散

 

英文论文摘要:

Nuclear localization of maspin is essential for its inhibition of tumor growth and metastasis

Maspin (mammary serine protease inhibitor or SerpinB5) acts as a tumor suppressor when overexpressed in aggressive cancer cell lines. However, its role in human cancer is controversial. Maspin expression has been associated with a poor prognosis in some studies, whereas in others, with favorable outcome. The clinical data suggest, however, that nuclear-localized maspin is associated with improved survival. We hypothesized that the tumor suppressor activity of maspin may require nuclear localization, and that the discordance between clinical and experimental reports is a consequence of the variable subcellular distribution of maspin. Furthermore, we surmized that nuclear maspin could function as a tumor suppressor through the regulation of genes involved in tumor growth and invasion. Maspin or maspin fused to a nuclear export signal were expressed in metastatic human breast and epidermoid carcinoma cell lines. We found that pan-cellular localized maspin inhibited in vivo tumor growth and metastasis when assessed in xenograft chicken embryo and murine mammary fat pad injection models. However, when maspin was excluded from the nucleus via a nuclear exclusion signal, it no longer functioned as a metastasis suppressor. Using chromatin immunoprecipitation, we show that nuclear maspin was enriched at the promoter of colony-stimulating factor-1 (CSF-1) and associated with diminished levels of CSF-1 mRNA. Our findings demonstrate that the nuclear localization of maspin is required for its tumor and metastasis suppressor functions in vivo, and suggest that its mechanism of action involves, in part, direct association of maspin with target genes.

 

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