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Expression of Laminin‐5 Enhances Tumorigenicity of Human Fibrosarcoma Cells in Nude Mice

机译:层粘连蛋白-5的表达增强了裸鼠的人纤维肉瘤细胞的致瘤性。

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摘要

Laminin‐5 (LN5), which consists of laminin α3, β3 and γ2 chains, is a laminin isoform produced by various kinds of normal epithelial cells and tumor cells. Strong activity of LN5 in adhesion, migration and scattering of cells in vitro and its frequent detection in human tumor tissues have suggested a possible role of LN5 in the malignant growth of tumor cells. To examine whether LN5 affects the malignant potential of tumor cells, we prepared human fibrosarcoma HT1080 cell lines producing LN5 by transfecting a cDNA of laminin α3 chain into the parent cell line, which constitutively expressed the laminin β3 and γ2 chains. The exogenous α3 chain associated with the endogenous β3 and γ2 chains to secrete the LN5 heterotrimer that has strong cell‐scattering and cell adhesion activities. The HT1080 transfectants expressing LN5 efficiently adhered to culture dishes in a serum‐free condition as compared with control HT1080 cells, which secreted the monomers and heterodimer of the β3 and γ2 chains. When injected into nude mice subcutaneously, the HT1080 transfectants expressing LN5 grew faster and formed much larger tumors than the control cells. This suggests that LN5 promotes tumor growth in vivo.
机译:Laminin-5(LN5)由层粘连蛋白α3,β3和γ2链组成,是由各种正常上皮细胞和肿瘤细胞产生的层粘连蛋白同工型。 LN5在体外细胞粘附,迁移和扩散中具有很强的活性,并且在人体肿瘤组织中的频繁检测表明LN5在肿瘤细胞的恶性生长中可能具有作用。为了检查LN5是否影响肿瘤细胞的恶性潜能,我们通过将层粘连蛋白α3链的cDNA转染到组成性表达层粘连蛋白β3和γ2链的亲本细胞系中,制备了产生LN5的人纤维肉瘤HT1080细胞系。与内源性β3和γ2链相关的外源性α3链分泌LN5异源三聚体,该异源三聚体具有很强的细胞散射和细胞粘附活性。与对照HT1080细胞相比,表达LN5的HT1080转染子可以有效地粘附在培养皿上,而对照HT1080细胞则分泌β3和γ2链的单体和异二聚体。当皮下注射到裸鼠体内时,表达LN5的HT1080转染子生长得比对照细胞快,并且形成的肿瘤要大得多。这表明LN5在体内促进肿瘤生长。

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