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Loss of maspin expression invasive potential in malig contributes to a more nant melanoma

机译:malig maspin表达侵袭力的丧失导致更自然的黑色素瘤

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Deregulation of protease expression and activity is known to play an important role in tumour progression of malignant melanoma. The serpin maspin, a tumour suppressor in breast and prostate cancer was described as an inhibitor of cell migration and inducer of cell adhesion between the basement membrane and extracellular matrix resulting in inhibition of tumour metastasis. In contrast, overexpression of maspin is correlated with poor prognosis in other cancers. However, little is known about expression, regulation and function of maspin in malignant melanoma. In this study, we found loss of maspin expression in malignant melanoma cells compared with normal human epidermal melanocytes, which was analysed by quantitative real-time PCR, Western blot analysis, immunohistochemistry and microarray. For functional studies, melanoma cell clones stably transfected with a maspin expression vector were tested for changes in proliferation, migration and invasion. Although we could not see differences in proliferation and migration, we detected strongly reduced invasive capacity in the melanoma cell clones in which maspin is re-expressed compared with control. Reduced invasive potential was also detected in three different melanoma cell lines transiently transfected with a maspin expression vector. Furthermore, exogenously added maspin alone was sufficient to reduce invasion in Mellm significantly, indicating that maspin directly inhibits invasion on the cell surface. In summary, we believe that maspin is a tumour suppressor in malignant melanoma.
机译:已知蛋白酶表达和活性的失调在恶性黑素瘤的肿瘤进展中起重要作用。 serpin maspin是乳腺癌和前列腺癌的肿瘤抑制因子,被描述为细胞迁移抑制剂和基底膜与细胞外基质之间细胞粘附的诱导剂,可抑制肿瘤转移。相反,maspin的过表达与其他癌症的不良预后相关。但是,关于maspin在恶性黑色素瘤中的表达,调控和功能的了解还很少。在这项研究中,我们发现与正常人表皮黑色素细胞相比,恶性黑色素瘤细胞中maspin表达缺失,这通过定量实时PCR,Western印迹分析,免疫组织化学和微阵列分析。对于功能研究,测试了用maspin表达载体稳定转染的黑素瘤细胞克隆的增殖,迁移和侵袭变化。尽管我们看不到增殖和迁移的差异,但我们发现,与对照相比,maspin重新表达的黑素瘤细胞克隆的侵袭能力大大降低。在用maspin表达载体瞬时转染的三种不同的黑色素瘤细胞系中,也检测到侵袭力降低。此外,单独添加外源Maspin足以显着减少Mellm的侵袭,表明maspin直接抑制细胞表面的侵袭。总而言之,我们认为maspin是恶性黑色素瘤的一种肿瘤抑制因子。

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