Galeazzi E, Olivero M, Gervasio F C, De Stefani A, Valente G, Comoglio P M, Di Renzo M F, Cortesina G
Department of Clinical Physiopathology, University of Turin School of Medicine, Italy.
Eur Arch Otorhinolaryngol. 1997;254 Suppl 1:S138-43. doi: 10.1007/BF02439745.
The c-MET oncogene encodes the receptor for hepatocyte growth factor/scatter factor (HGF/SF), which is known to stimulate the invasive growth of epithelial cells cultured in vitro. The Met/HGF receptor is a heterodimeric transmembrane tyrosine kinase, which is a prototype for a new family of growth factor receptors. The c-MET oncogene is expressed in several types of epithelial tissue including keratinocytes and is over-expressed in a number of human carcinomas. Studies on various carcinoma cell lines have shown that over-expression and structural alteration of the receptor result in its activation and confer tumorigenesis. We have studied Met/HGF receptor expression in tissue specimens from 34 patients with head and neck squamous cell carcinomas (HNSCC) and in 17 regional lymph node metastases. Western blot analysis was employed, using monoclonal antibodies directed against either the intracellular or extracellular domain of the receptor. Each sample was compared to its normal counterpart. The receptor did not show any major structural alterations in HNSCC tissues, but its expression was increased from 2- to 50-fold in about 70% of tumors. Immunohistochemistry then showed that the same antibodies stained only a few cells in the basal layer of normal squamous epithelium but intensely marked tumor cells. In the lymph node metastases of Met-positive tumors, receptor expression was maintained and sometimes increased with respect to primary tumors. Immunohistochemical analysis of the metastatic lymph nodes showed that cells were negative in the normal lymphatic tissue and strongly stained in tumor cells. Over-expression of the Met/HGF receptor was found at all tumor stages but was more significant in those associated with enlarged or multiple (N2-N3) lymph node metastases. These data show that expression of the Met/HGF receptor may be involved in the progression of HNSCC towards a metastatic phenotype and may be a useful marker of head and neck tumor cell spread to regional lymph nodes.
c-MET癌基因编码肝细胞生长因子/分散因子（HGF/SF）的受体，已知该因子可刺激体外培养的上皮细胞的侵袭性生长。Met/HGF受体是一种异二聚体跨膜酪氨酸激酶，是一类新的生长因子受体的原型。c-MET癌基因在包括角质形成细胞在内的多种上皮组织中表达，并在许多人类癌症中过度表达。对各种癌细胞系的研究表明，受体的过度表达和结构改变会导致其激活并引发肿瘤发生。我们研究了34例头颈部鳞状细胞癌（HNSCC）患者组织标本及17例区域淋巴结转移灶中Met/HGF受体的表达。采用蛋白质免疫印迹分析，使用针对受体细胞内或细胞外结构域的单克隆抗体。将每个样本与其正常对应物进行比较。在HNSCC组织中，受体未显示任何主要结构改变，但其表达在约70%的肿瘤中增加了2至50倍。免疫组织化学显示，相同抗体仅对正常鳞状上皮基底层的少数细胞染色，但对肿瘤细胞有强烈染色。在Met阳性肿瘤的淋巴结转移灶中，受体表达得以维持，有时相对于原发肿瘤还会增加。对转移性淋巴结的免疫组织化学分析显示，正常淋巴组织中的细胞呈阴性，而肿瘤细胞呈强染色。在所有肿瘤阶段均发现Met/HGF受体过度表达，但在伴有肿大或多个（N2-N3）淋巴结转移的肿瘤中更为显著。这些数据表明，Met/HGF受体的表达可能参与HNSCC向转移表型的进展，可能是头颈部肿瘤细胞向区域淋巴结扩散的有用标志物。
