Coexpression of hepatocyte growth factor and c-Met proto-oncogene product in synovial sarcoma

Coexpression of hepatocyte growth factor and c-Met proto-oncogene product in synovial sarcoma
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DOI:
10.1111/j.1440-1827.1998.tb03836.x
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发表时间:
1998-10-01
影响因子:
2.2
通讯作者:
Machinami, R
Machinami, R
中科院分区:
医学4区
文献类型:
--
作者:
Motoi, T;Ishida, T;Machinami, R

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肝细胞生长因子(HGF)是一种异二聚体多肽生长因子,具有丝裂原、运动原和形态原的多种作用,HGF受体的特征是c-Met原癌基因产物(c-Met),是一种异二聚体酪氨酸激酶受体,由于HGF是由间质细胞产生的,而c-Met主要在各种上皮细胞上表达,因此肝细胞生长因子在间质组织和上皮组织之间起着中介作用。HGF/c-Met系统在胚胎发生和各种器官的再生中起重要作用,滑膜肉瘤(SS)是类人猿特有的表现为上皮分化的肉瘤,但对其组织发生机制知之甚少。采用免疫组化方法检测了12例(双相型和单相纤维型各6例)SS标本中HGF和c-Met的表达,5例双相型SS的上皮成分中HGF和c-Met共表达,而3例单相纤维型SS的上皮样巢中仅c-Met表达,梭形细胞成分中HGF和c-Met阴性,在SS中上皮标志物阳性。细胞角蛋白和上皮膜抗原在上皮成分中弥散可见,在梭形细胞中局部可见,而波形蛋白主要在梭形细胞成分中阳性。表达HGF和c-Met的区域对应不同的上皮结构;然而,HGF和c-Met在SS梭形细胞组分中未在其他表达上皮标志物的肿瘤细胞中表达。考虑到HGF的形态发生作用,这是其最重要的作用之一,HGF和c-Met在SS中独特的免疫组织化学定位提示HGF/c-Met系统可能与双相SS中上皮(腺)结构的形成密切相关。
Hepatocyte growth factor (HGF) is a heterodimeric polypeptide growth factor that has pleiotropic roles, including those of mitogen, motogen and morphogen, The HGF receptor is characterized as a c-Met proto-oncogene product (c-Met), which is a heterodimeric tyrosine kinase receptor, Hepatocyte growth factor acts as a mediator between the mesenchymal and epithelial tissues because HGF is produced by mesenchymal cells and c-Met is mainly expressed on various epithelial cells, Furthermore, the HGF/c-Met system plays an important role in embryogenesis and the regeneration of various organs, Synovial sarcoma (SS) ape unique sarcoma that show epithelial differentiation, but little is known about their histogenesis. The expression of HGF and c-Met was examined by immunohistochemistry in SS specimens from 12 patients (six each of biphasic and monophasic fibrous types), Immunohistochemical coexpression of HGF and c-Met was demonstrated in the epithelial component of five biphasic SS, while only c-Met was expressed in the epithelioid nests of three monophasic fibrous SS, The spindle cell component was negative for HGF and c-Met, In SS, positivity for epithelial markers, such as cytokeratins and epithelial membrane antigen, was diffusely observed in the epithelial component and was focally observed in spindle cells, while vimentin was positive predominantly in the spindle cell component. The areas expressing HGF and c-Met corresponded to distinct epithelial structures; however, HGF and c-Met expression were not found in any other tumor cells expressing epithelial markers in the spindle cell component of SS, Considering the morphogenic effect of HGF, which has been known to be one of its most important roles, the unique immunohistochemical localization of HGF and c-Met in SS suggests that the HGF/c-Met system may be closely related to the formation of epithelial (glandular) structures in biphasic SS.