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层粘连蛋白-411 和 -511 调节胃癌细胞的增殖、黏附和形态。

Laminin-411 and -511 Modulate the Proliferation, Adhesion, and Morphology of Gastric Cancer Cells.

机构信息

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.

Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.

出版信息

Cell Biochem Biophys. 2021 Jun;79(2):407-418. doi: 10.1007/s12013-021-00972-3. Epub 2021 Feb 25.

Abstract

Laminins (Ln), a type of extracellular matrix glycoprotein, are key regulators of cellular behavior. Recent work revealed that in various tumor cell lines, laminin isoforms influence specific responses, such as cell anchorage, survival, proliferation, migration, organization, and specialization. The contribution of laminin isoforms to the function of gastric cancer cells, however, remain unclear. Here, we revealed that in gastric cancer, laminin isoforms Ln411, Ln421, Ln511, and Ln521 promote cellular proliferation; Ln511 and Ln521 increase cell cytoplasmic volume; Ln511 hampers invadopodia formation in some cells, Ln511 enables prompt adhesion of cells to plates, and Ln411 and Ln511 do not alter the gastric cancer stem cell markers CD44 and Lgr5. These results indicate that Ln411 and Ln511 dynamically modulate the proliferation, adhesion, and morphology of gastric cancer cells in different ways that are independent of stem cell properties. In particular, Ln511 showed a high affinity for gastric cancer cells. Our observations broaden the possible options for controlling cancer cell progression and metastasis by modulating laminin-integrin interactions.

摘要

层粘连蛋白(Ln)是细胞外基质糖蛋白的一种,是细胞行为的关键调节因子。最近的研究工作表明,在各种肿瘤细胞系中,层粘连蛋白亚型影响特定的反应,如细胞附着、存活、增殖、迁移、组织和特化。然而,层粘连蛋白亚型对胃癌细胞功能的贡献尚不清楚。在这里,我们揭示了在胃癌中,层粘连蛋白亚型 Ln411、Ln421、Ln511 和 Ln521 促进细胞增殖;Ln511 和 Ln521 增加细胞胞质体积;Ln511 抑制某些细胞中侵袭伪足的形成,Ln511 使细胞迅速黏附于平板上,而 Ln411 和 Ln511 不改变胃癌干细胞标志物 CD44 和 Lgr5。这些结果表明,Ln411 和 Ln511 以不同的方式动态调节胃癌细胞的增殖、黏附和形态,而不改变干细胞特性。特别是,Ln511 对胃癌细胞表现出高亲和力。我们的观察结果拓宽了通过调节层粘连蛋白-整合素相互作用来控制癌细胞进展和转移的可能选择。

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