Loss of LSR affects epithelial barrier integrity and tumor xenograft growth of CaCo-2 cells.
Loss of LSR affects epithelial barrier integrity and tumor xenograft growth of CaCo-2 cells.
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DOI：
10.18632/oncotarget.10425
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发表时间：
2017-06-06
期刊：
影响因子：
--
通讯作者：
Papatheodorou P
中科院分区：
文献类型：
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作者：
Czulkies BA;Mastroianni J;Lutz L;Lang S;Schwan C;Schmidt G;Lassmann S;Zeiser R;Aktories K;Papatheodorou P
脂解刺激的脂蛋白受体（LSR）是一种脂蛋白受体，作为I型梭菌样毒素的宿主受体，并参与三细胞接触的形成。特别令人感兴趣的是LSR在各种癌症进展中的作用。在这里，我们的目的是研究LSR缺陷的结肠癌衍生的细胞系HCT 116和CaCo-2在小鼠异种移植模型中的肿瘤生长。尽管LSR的敲除对HCT 116细胞的肿瘤生长没有影响，但我们观察到CaCo-2 LSR敲除肿瘤生长到比其野生型对应物更小的尺寸。组织学分析显示，在源自LSR缺陷型CaCo-2细胞的肿瘤中，凋亡和坏死细胞死亡增加。LSR缺陷型CaCo-2细胞在体外表现出细胞增殖增加和上皮形态改变，三纤维素靶向三细胞接触受损。此外，LSR的损失降低了CaCo-2细胞单层的跨上皮电阻，并增加了小分子的渗透性。此外，LSR缺陷型CaCo-2细胞在3D培养中形成的囊肿比野生型细胞更大。我们的研究提供了证据表明LSR影响CaCo-2细胞的上皮形态和屏障形成，并首次研究了LSR缺乏对结肠癌衍生细胞系肿瘤生长特性的影响。
The lipolysis-stimulated lipoprotein receptor (LSR) is a lipoprotein receptor, serves as host receptor for clostridial iota-like toxins and is involved in the formation of tricellular contacts. Of particular interest is the role of LSR in progression of various cancers. Here we aimed to study the tumor growth of LSR-deficient colon carcinoma-derived cell lines HCT116 and CaCo-2 in a mouse xenograft model. Whereas knockout of LSR had no effect on tumor growth of HCT116 cells, we observed that CaCo-2 LSR knockout tumors grew to a smaller size than their wild-type counterparts. Histological analysis revealed increased apoptotic and necrotic cell death in a tumor originating from LSR-deficient CaCo-2 cells. LSR-deficient CaCo-2 cells exhibited increased cell proliferation in vitro and an altered epithelial morphology with impaired targeting of tricellulin to tricellular contacts. In addition, loss of LSR reduced the transepithelial electrical resistance of CaCo-2 cell monolayers and increased permeability for small molecules. Moreover, LSR-deficient CaCo-2 cells formed larger cysts in 3D culture than their wild-type counterparts. Our study provides evidence that LSR affects epithelial morphology and barrier formation in CaCo-2 cells and examines for the first time the effects of LSR deficiency on the tumor growth properties of colon carcinoma-derived cell lines.