Expression of HGF/SF in mesothelioma cell lines and its effects on cell motility, proliferation and morphology.
Expression of HGF/SF in mesothelioma cell lines and its effects on cell motility, proliferation and morphology.
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DOI：
10.1038/bjc.1998.176
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发表时间：
1998-04
影响因子：
8.8
通讯作者：
Warn, R M
中科院分区：
文献类型：
--
作者：
Harvey, P;Warn, A;Dobbin, S;Arakaki, N;Daikuhara, Y;Jaurand, M C;Warn, R M
肝细胞生长因子/散射因子（HGF/SF）的表达进行了研究，在12间皮瘤细胞系的特点是无论是上皮样或成纤维细胞样表型。通过生物测定和ELISA分析来自这些细胞系的条件培养基，并且在三个细胞系中检测到HGF/SF，所有细胞系均具有成纤维细胞样或混合形态。没有8个上皮样细胞系表达该因子。因此，对于这些细胞系，分泌HGF/SF的能力与细胞表型相关。根据这些观察结果，进一步研究了分别具有成纤维细胞样和上皮样表型的两种细胞系BR和BT。两种细胞系均表达Met受体，但仅BR分泌HGF/SF。两种细胞系对外源性HGF/SF处理的形态学变化作出反应，但方式不同：BR变得更加细长和双极，而BT形成更多的扩散细胞集落。HGF/SF对上皮样BT细胞起旁分泌作用，刺激细胞铺展和增殖。有趣的是，BT细胞扩散，但没有分散在外源性HGF/SF的反应。相反，BR细胞显示HGF/SF仅对细胞运动性有一些刺激，并且未观察到细胞增殖增加。由于HGF/SF以前被发现在恶性间皮瘤患者的胸腔积液液和石蜡包埋的肿瘤组织中，它的结论是，HGF/SF可以很好地刺激恶性间皮瘤在体内的生长和扩散的旁分泌和/或自分泌机制。
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.