Dobashi Yoh, Watanabe Hideomi, Matsubara Maki, Yanagawa Takashi, Raz Avraham, Shimamiya Tamiyasu, Ooi Akishi
Department of Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
J Pathol. 2006 Jan;208(1):44-53. doi: 10.1002/path.1878.
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.
为了评估自分泌运动因子（AMF）在间充质肿瘤中的作用，对骨与软组织的肿瘤、肿瘤样病变及其他病变中的AMF蛋白和mRNA表达进行了分析。对200例病例的免疫组织化学分析显示，72.5%的病例呈阳性染色，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显示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，除皮肤纤维瘤/隆突性皮肤纤维肉瘤外，恶性肿瘤中AMF的表达高于同一组织病理学谱系的良性肿瘤。然而，mRNA水平与蛋白水平不一致，mRNA表达较高而蛋白表达较低的肉瘤显示出远处转移的趋势。在培养细胞中，AMF分泌到条件培养基中并可被检测到。此外，为了检测周转率的变化而向细胞中添加蛋白酶体抑制剂时，这些化合物并未显著改变细胞内AMF蛋白的水平。基于这些总体发现，提示特定亚型的肉瘤分泌AMF，而非以更高的周转率降解该蛋白。这种分泌的AMF可能通过自分泌作用增强其细胞运动性，并最终导致转移潜能增加。总的来说，在间充质组织的广泛病变中均观察到AMF，支持其参与包括增殖、分化、代谢和转移在内的多种细胞功能的观点。此外，其mRNA的高表达可能表明蛋白分泌水平较高，并界定了一组具有高转移潜能的特别侵袭性的肿瘤。
