Rees Helen, Williamson Daniel, Papanastasiou Antigoni, Jina Nipurna, Nabarro Steven, Shipley Janet, Anderson John
Unit of Molecular Haematology and Cancer Biology, Institute of Child Health, London, WC1N 1EH, UK.
Growth Factors. 2006 Sep;24(3):197-208. doi: 10.1080/08977190600759923.
The receptor tyrosine kinase MET and its ligand hepatocyte growth factor (HGF), have been implicated in the genesis of the paediatric tumour rhabdomyosarcoma (RMS). Addition of exogenous HGF to RH30 RMS cells enhanced non-chemotactic migration. Stable transfection of dominant negative MET into RH30 cells attenuated Matrigel invasion and in vivo tumour growth. To assess the role of a putative HGF-MET pathway in human RMS, we measured their expression in a panel of 68 human primary tumours. All tumours expressed MET but with a three orders of magnitude variation of expression and 62% of tumours co-expressed HGF. In contrast with other tumour types, neither high-MET expression nor HGF/MET coexpression correlated with metastatic disease. In a microarray screen, we identified CCN1 as being 7.8-fold up regulated following addition of HGF to RH30 cells and in RMS tumours, CCN1 expression correlated with HGF expression. Surprisingly, we identified MET as a consistent feature of embryonal and not alveolar RMS.
受体酪氨酸激酶MET及其配体肝细胞生长因子（HGF）与小儿肿瘤横纹肌肉瘤（RMS）的发生有关。将外源性HGF添加到RH30 RMS细胞中可增强非趋化性迁移。将显性负性MET稳定转染到RH30细胞中可减弱基质胶侵袭和体内肿瘤生长。为了评估假定的HGF-MET途径在人RMS中的作用，我们在一组68例人原发性肿瘤中测量了它们的表达。所有肿瘤均表达MET，但表达量有三个数量级的差异，62%的肿瘤共表达HGF。与其他肿瘤类型不同，高MET表达和HGF/MET共表达均与转移性疾病无关。在微阵列筛选中，我们发现添加HGF到RH30细胞后，CCN1上调7.8倍，并且在RMS肿瘤中，CCN1表达与HGF表达相关。令人惊讶的是，我们发现MET是胚胎性而非肺泡性RMS的一个一致特征。
