Harvey P, Warn A, Dobbin S, Arakaki N, Daikuhara Y, Jaurand M C, Warn R M
School of Biology, University of East Anglia, Norwich, UK.
Br J Cancer. 1998 Apr;77(7):1052-9. doi: 10.1038/bjc.1998.176.
The expression of hepatocyte growth factor/scatter factor (HGF/SF) was studied in 12 mesothelioma cell lines characterized by either an epithelioid or a fibroblast-like phenotype. Conditioned media from these lines were analysed by bioassay and ELISA, and HGF/SF was detected in three cell lines, all with a fibroblast-like or mixed morphology. None of eight epithelioid cell lines expressed the factor. Thus, for these cell lines, the ability to secrete HGF/SF correlated with the cell phenotype. Following on from these observations, two cell lines, BR and BT, with a fibroblast-like and an epithelioid phenotype, respectively, were further investigated. Both cell lines expressed the Met receptor but only BR secreted HGF/SF. Both cell lines responded to exogenous HGF/SF treatment by a change of morphology but in different ways: BR became more elongated and bipolar, while BT formed more spread-out cell colonies. HGF/SF acted as a paracrine effector on the epithelioid BT cells and stimulated both cell-spreading and proliferation. Interestingly, BT cells spread but did not scatter in response to exogenous HGF/SF. In contrast BR cells showed only some stimulation of cell motility with HGF/SF and no increase in cell proliferation was observed. Because HGF/SF was previously found in the pleural effusion fluids of patients with malignant mesothelioma and in paraffin-embedded tumour tissues, it is concluded that HGF/SF may well stimulate the growth and spread of malignant mesothelioma in vivo by paracrine and/or autocrine mechanisms.
在12种具有上皮样或成纤维细胞样表型特征的间皮瘤细胞系中研究了肝细胞生长因子/分散因子（HGF/SF）的表达。通过生物测定法和酶联免疫吸附测定法分析了这些细胞系的条件培养基，在3种细胞系中检测到HGF/SF，所有这些细胞系均具有成纤维细胞样或混合形态。8种上皮样细胞系均未表达该因子。因此，对于这些细胞系，分泌HGF/SF的能力与细胞表型相关。基于这些观察结果，进一步研究了两种细胞系，分别为具有成纤维细胞样表型的BR和具有上皮样表型的BT。两种细胞系均表达Met受体，但只有BR分泌HGF/SF。两种细胞系对外源性HGF/SF处理均有形态变化反应，但方式不同：BR变得更加细长且呈双极状，而BT形成更多分散的细胞集落。HGF/SF作为旁分泌效应物作用于上皮样BT细胞，刺激细胞铺展和增殖。有趣的是，BT细胞对外源性HGF/SF有铺展反应，但没有分散。相比之下，BR细胞仅在HGF/SF作用下细胞运动略有刺激，未观察到细胞增殖增加。由于先前在恶性间皮瘤患者的胸腔积液和石蜡包埋的肿瘤组织中发现了HGF/SF，因此得出结论，HGF/SF很可能通过旁分泌和/或自分泌机制在体内刺激恶性间皮瘤的生长和扩散。
