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血小板衍生生长因子(PDGF)BB通过血小板衍生生长因子受体β-整合素α3β1相互作用,对人恶性间皮瘤细胞起趋化因子的作用。

Platelet-derived growth factor (PDGF) BB acts as a chemoattractant for human malignant mesothelioma cells via PDGF receptor beta-integrin alpha3beta1 interaction.

作者信息

Klominek J, Baskin B, Hauzenberger D

机构信息

Department of Lung Medicine, Karolinska Institute at Huddinge Hospital, Sweden.

出版信息

Clin Exp Metastasis. 1998 Aug;16(6):529-39. doi: 10.1023/a:1006542301794.

Abstract

Platelet-derived growth factor BB (PDGF BB) and the PDGF receptor beta are expressed on mesothelioma cells, but their biological function has not yet been defined. In the present study we used Boyden chambers fitted with filters coated with the adhesive matrix proteins fibronectin, laminin, collagen type IV or the nonmatrix adhesive molecule poly-L-lysine (PLL). Mesothelioma cells migrated towards PDGF BB at concentrations ranging from 0.78 to 12.5 ng/ml if matrix proteins were present as adhesive substrates. This migration was integrin dependent since the same cells failed to migrate if the adhesive interactions necessary for migration were provided by molecules other than integrins. Migration of mesothelioma cells on fibronectin, laminin or collagen-type IV in response to PDGF BB was inhibited if the cells were pretreated with blocking antibodies to alpha3beta1 integrin. These findings describe for the first time PDGF BB as a chemoattractant for malignant mesothelioma cells and that collaboration between PDGF receptor beta and integrin alpha3beta1 is necessary for the motile response of these cells to PDGF BB.

摘要

血小板衍生生长因子BB(PDGF BB)和PDGF受体β在间皮瘤细胞上表达,但其生物学功能尚未明确。在本研究中,我们使用了装有涂有黏附基质蛋白纤连蛋白、层粘连蛋白、IV型胶原或非基质黏附分子聚-L-赖氨酸(PLL)的滤膜的Boyden小室。如果存在基质蛋白作为黏附底物,间皮瘤细胞会朝着浓度范围为0.78至12.5 ng/ml的PDGF BB迁移。这种迁移是整合素依赖性的,因为如果迁移所需的黏附相互作用由整合素以外的分子提供,相同的细胞就无法迁移。如果用针对α3β1整合素的阻断抗体对细胞进行预处理,间皮瘤细胞在纤连蛋白、层粘连蛋白或IV型胶原上对PDGF BB的迁移反应就会受到抑制。这些发现首次将PDGF BB描述为恶性间皮瘤细胞的趋化因子,并且PDGF受体β与整合素α3β1之间的协作对于这些细胞对PDGF BB的运动反应是必需的。

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