Enforced Expression of METCAM/MUC18 Increases Tumorigenesis of Human Prostate Cancer LNCaP Cells in Nude Mice
Enforced Expression of METCAM/MUC18 Increases Tumorigenesis of Human Prostate Cancer LNCaP Cells in Nude Mice
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DOI：
10.1016/j.juro.2010.11.052
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发表时间：
2011-04-01
影响因子：
6.6
通讯作者：
Liu, Yuan
中科院分区：
文献类型：
--
作者：
Wu, Guang-Jer;Wu, Mei-Whey H.;Liu, Yuan
目的：转移细胞黏附分子/MUC18是Ig样基因超家族中的一个细胞黏附分子，是前列腺癌细胞进展的关键决定因素。然而，人类转移细胞黏附分子/MUC18刺激肿瘤进展的机制尚不清楚。为了探讨人转移细胞黏附分子/MUC18是否可能作为一种肿瘤进展基因，我们研究了其增强表达对LNCaP细胞成瘤的影响。材料和方法：将表达LNCaP克隆的转移细胞黏附分子/MUC18与Matrigel T联合皮下注射到裸鼠体内，观察这些细胞的成瘤情况，并在不同时间测量肿瘤。为了了解其机制，我们还检测了转移细胞黏附分子/MUC18下游几个关键效应因子在皮下肿瘤中的表达，并与以前获得的原位(前列腺)肿瘤的表达进行了比较。结果：表达LNCaP克隆/细胞的人转移细胞黏附分子/MUC18的肿瘤比转染空载体的克隆/细胞早18天出现。增强表达人转移细胞黏附分子/MUC18还可使肿瘤体积增加2倍，成瘤性增加10~12倍，最终肿瘤重量增加5倍。增强表达使细胞增殖指数Ki67、增殖细胞核抗原、存活指数磷酸化AKT、血管生成指数血管内皮生长因子、血管内皮生长因子受体2和CD31水平升高。结论：人转移细胞黏附分子/MUC18的增强表达可促进体内前列腺癌的发生，可能通过促进细胞增殖、上调AKT生存通路、增强细胞的血管生成能力来影响这一过程。
Purpose: Metastasis cell adhesion molecule/MUC18, a cell adhesion molecule in the Ig-like gene super family, is a key determinant in prostate cancer cell progression. However, the mechanisms by which human metastasis cell adhesion molecule/MUC18 stimulates progression are poorly understood. To investigate this and determine whether human metastasis cell adhesion molecule/MUC18 may act as a possible tumor progression gene, we studied the effect of its enforced expression on LNCaP cell tumorigenesis.Materials and Methods: We subcutaneously co-injected a metastasis cell adhesion molecule/MUC18 expressing LNCaP clone and control clones/cells with Matrigel T into nude mice, observed tumor formation of these cells and measured tumors at different times. To understand the mechanisms we also determined the expression of several downstream key effectors of metastasis cell adhesion molecule/MUC18 in subcutaneous tumors and compared them to those in previously obtained orthotopic (prostatic) tumors.Results: Tumors derived from human metastasis cell adhesion molecule/MUC18 expressing LNCaP clones/cells appeared about 18 days earlier than the empty vector transfected clone/cells. Enforced expression of human metastasis cell adhesion molecule/MUC18 also increased tumor take 2-fold, tumorigenicity 10 to 12-fold and final tumor weight 5-fold. Enforced expression appeared to render the cells with increased levels of the proliferation indexes Ki67 and proliferating cell nuclear antigen, the survival index phospho-AKT, and the angiogenesis indexes vascular endothelial growth factor, vascular endothelial growth factor receptor 2 and CD31. However, it did not significantly render the cells with altered levels of various apoptosis indexes.Conclusions: Enforced expression of human metastasis cell adhesion molecule/MUC18 increases prostate tumorigenesis in vivo and may affect the process by increasing proliferation, up-regulating the AKT survival pathway, and augmenting the angiogenic ability of prostate cancer cells.