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抗LRP/LR特异性抗体IgG1-iS18可抑制肝癌细胞的黏附和侵袭。

Anti-LRP/LR specific antibody IgG1-iS18 impedes adhesion and invasion of liver cancer cells.

作者信息

Chetty Carryn, Khumalo Thandokuhle, Da Costa Dias Bianca, Reusch Uwe, Knackmuss Stefan, Little Melvyn, Weiss Stefan F T

机构信息

School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Gauteng, The Republic of South Africa (RSA).

Affimed Therapeutics AG, Technologiepark, Im Neuenheimer Feld, Heidelberg, Baden-Wuerttemberg, Germany.

出版信息

PLoS One. 2014 May 5;9(5):e96268. doi: 10.1371/journal.pone.0096268. eCollection 2014.

Abstract

Two key events, namely adhesion and invasion, are pivotal to the occurrence of metastasis. Importantly, the 37 kDa/67 kDa laminin receptor (LRP/LR) has been implicated in enhancing these two events thus facilitating cancer progression. In the current study, the role of LRP/LR in the adhesion and invasion of liver cancer (HUH-7) and leukaemia (K562) cells was investigated. Flow cytometry revealed that the HUH-7 cells displayed significantly higher cell surface LRP/LR levels compared to the poorly-invasive breast cancer (MCF-7) control cells, whilst the K562 cells displayed significantly lower cell surface LRP/LR levels in comparison to the MCF-7 control cells. However, Western blotting and densitometric analysis revealed that all three tumorigenic cell lines did not differ significantly with regards to total LRP/LR levels. Furthermore, treatment of liver cancer cells with anti-LRP/LR specific antibody IgG1-iS18 (0.2 mg/ml) significantly reduced the adhesive potential of cells to laminin-1 and the invasive potential of cells through the ECM-like Matrigel, whilst leukaemia cells showed no significant differences in both instances. Additionally, Pearson's correlation coefficients suggested direct proportionality between cell surface LRP/LR levels and the adhesive and invasive potential of liver cancer and leukaemia cells. These findings suggest the potential use of anti-LRP/LR specific antibody IgG1-iS18 as an alternative therapeutic tool for metastatic liver cancer through impediment of the LRP/LR- laminin-1 interaction.

摘要

两个关键事件,即黏附和侵袭,对于转移的发生至关重要。重要的是,37 kDa/67 kDa层粘连蛋白受体(LRP/LR)与增强这两个事件有关,从而促进癌症进展。在本研究中,研究了LRP/LR在肝癌(HUH-7)和白血病(K562)细胞黏附和侵袭中的作用。流式细胞术显示,与侵袭性较差的乳腺癌(MCF-7)对照细胞相比,HUH-7细胞的细胞表面LRP/LR水平显著更高,而与MCF-7对照细胞相比,K562细胞的细胞表面LRP/LR水平显著更低。然而,蛋白质印迹法和光密度分析显示,所有三种致瘤细胞系在总LRP/LR水平方面没有显著差异。此外,用抗LRP/LR特异性抗体IgG1-iS18(0.2 mg/ml)处理肝癌细胞显著降低了细胞与层粘连蛋白-1的黏附潜力以及细胞通过类细胞外基质基质胶的侵袭潜力,而白血病细胞在这两种情况下均无显著差异。此外,皮尔逊相关系数表明细胞表面LRP/LR水平与肝癌和白血病细胞的黏附及侵袭潜力之间呈正比。这些发现表明,抗LRP/LR特异性抗体IgG1-iS18可能通过阻碍LRP/LR-层粘连蛋白-1相互作用,作为转移性肝癌的一种替代治疗工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7afa/4010454/9c78c22a3730/pone.0096268.g001.jpg

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