Autocrine motility factor/glucose-6-phosphate isomerase is a possible predictor of metastasis in bone and soft tissue tumours

Autocrine motility factor/glucose-6-phosphate isomerase is a possible predictor of metastasis in bone and soft tissue tumours
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DOI:
10.1002/path.1878
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发表时间:
2006-01-01
影响因子:
7.3
通讯作者:
Ooi, A
Ooi, A
中科院分区:
医学1区
文献类型:
--
作者:
Dobashi, Y;Watanabe, H;Ooi, A

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为了评估自分泌运动因子(AMF)在间充质肿瘤中的作用,我们分析了肿瘤、肿瘤样病变以及其他骨和软组织病变中AMF蛋白和mRNA的表达。免疫组化分析200例,阳性染色率为72.5%,提示AMF是一种广泛表达的蛋白。脊索样、软骨样和肌肉肿瘤在良性和恶性肿瘤中均表现出较高的免疫反应性。免疫印迹分析证实了免疫组织化学的结果。一般来说,恶性肿瘤的AMF表达高于良性肿瘤,但皮肤纤维瘤/皮肤纤维肉瘤隆突除外。然而,mRNA水平与蛋白水平并不一致,mRNA水平较高而蛋白水平较低的肉瘤有远处转移的趋势。在培养细胞中,AMF在条件培养基中分泌和检测。此外,当将蛋白酶体抑制剂添加到细胞中以检查周转率的变化时,这些化合物并没有显着改变细胞内AMF蛋白的水平。在这些总体发现的基础上,这表明一个特定的肉瘤亚群分泌AMF,而不是以更高的周转率降解这种蛋白质。这种分泌的AMF可能通过自分泌作用增强其细胞运动性,并最终导致转移潜力增加。总的来说,AMF在间充质组织的广泛病变中被观察到,支持了它参与多种细胞功能的概念,包括增殖、分化、代谢和转移。此外,其mRNA的高表达可能表明蛋白质分泌水平较高,并定义了具有高转移潜力的特别侵袭性肿瘤组。版权所有(c) 2005大不列颠和爱尔兰病理学会。约翰·威利父子有限公司出版。
In order to assess the involvement of autocrine motility factor (AMF) in mesenchymal tumours, AMF protein and mRNA expression was analysed in tumours, tumour-like lesions, and other lesions of bone and soft tissue. Immunohistochemical analysis of 200 cases revealed positive staining in 72.5% of the cases, suggesting that AMF is a widely expressed protein. Chordoid, chondroid, and muscular tumours revealed higher immunoreactivity in both benign and malignant tumours. Immunoblotting analysis corroborated the results of immunohistochemistry. Generally, malignant tumours revealed higher expression of AMF than benign tumours of the same histopathological lineage, except for dermatofibroma/dermatofibrosarcoma protuberans. However, mRNA levels were not concordant with protein levels, and sarcomas that displayed higher mRNA and lower protein expression levels showed a trend for distant metastasis. In cultured cells, AMF was secreted and detected in conditioned culture medium. Furthermore, when proteasome inhibitors were added to cells in order to examine the changes in turnover rates, these compounds did not significantly alter the intracellular levels of AMF protein. On the basis of these overall findings, it is suggested that a particular subset of sarcomas secrete AMF, rather than degrading this protein at a higher turnover rate. This secreted AMF presumably enhances their cell motility through an autocrine effect and eventually causes increased metastatic potential. Collectively, AMF was observed in a wide spectrum of lesions of mesenchymal tissue, supporting the notion that it is involved in various cellular functions, including proliferation, differentiation, metabolism, and metastasis. In addition, higher expression of its mRNA may indicate higher levels of protein secretion and define a particularly aggressive group of tumours with high metastatic potential. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.