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CD146 和 latexin 在甲状腺癌不同阶段的临床意义。

Clinical significance of CD146 and latexin during different stages of thyroid cancer.

机构信息

Tulane University Health Sciences Center, New Orleans, LA 70112, USA.

出版信息

Mol Cell Biochem. 2013 Sep;381(1-2):95-103. doi: 10.1007/s11010-013-1691-x. Epub 2013 May 28.

Abstract

Molecular mechanisms underlying thyroid tumorigenesis and identifying new therapeutic targets are still under investigation. We aim to investigate the role of CD146 and latexin (Lxn) and examine whether they have any clinical significance in thyroid cancer. Human thyroid papillary (PTC), follicular (FTC), anaplastic (ATC) cancer cells, and other control cells were used in this study. Western blot, cell proliferation, invasion assay, and shRNA were applied to study the expression levels and functional significances of CD146 and Lxn in thyroid cells. The protein expression was evaluated by immunohistochemistry using human tissue microarray (TMA) slides. Multivariate analysis was used to examine whether these proteins have any clinical significance in patients with thyroid cancer. The protein expressions of CD146 and Lxn were detected in most thyroid cancer cell lines when compared with normal cells. Notably, knockdown of CD146 reduced the migration and invasion in K1 (PTC) and OCUT-1 (ATC) cells. TMAs showed more immunoreactivity against CD146 and Lxn in PTC cores compared with FTC, ATC, and normal tissues. A positive correlation was established between CD146 and both Lxn (r = 0.421, p = 0.045) and age (r = 0.566, p = 0.012); however, it showed a negative correlation with tumor stage (r = -0.231, p = 0.010). In conclusion, CD146 and Lxn increased tumor migration and invasion in vitro and showed a high expression in PTC compared to those in ATC and normal human tissues demonstrating their role in early stage of thyroid tumorigenesis. CD146 was positively correlated with age, but negatively correlated with tumor stage.

摘要

甲状腺肿瘤发生的分子机制和新的治疗靶点的鉴定仍在研究中。我们旨在研究 CD146 和 latexin(Lxn)的作用,并探讨它们在甲状腺癌中的临床意义。本研究使用了人甲状腺乳头状癌(PTC)、滤泡癌(FTC)、间变性癌(ATC)癌细胞和其他对照细胞。应用 Western blot、细胞增殖、侵袭实验和 shRNA 研究 CD146 和 Lxn 在甲状腺细胞中的表达水平和功能意义。使用人组织微阵列(TMA)载玻片通过免疫组织化学评估蛋白质表达。采用多变量分析检查这些蛋白质在甲状腺癌患者中的临床意义。与正常细胞相比,大多数甲状腺癌细胞系中检测到 CD146 和 Lxn 的蛋白表达。值得注意的是,CD146 的敲低减少了 K1(PTC)和 OCUT-1(ATC)细胞的迁移和侵袭。TMA 显示 PTC 核心中 CD146 和 Lxn 的免疫反应性明显高于 FTC、ATC 和正常组织。CD146 与 Lxn(r = 0.421,p = 0.045)和年龄(r = 0.566,p = 0.012)呈正相关;然而,它与肿瘤分期呈负相关(r = -0.231,p = 0.010)。总之,CD146 和 Lxn 增加了体外肿瘤的迁移和侵袭,并在 PTC 中表达高于 ATC 和正常人类组织,表明它们在甲状腺肿瘤发生的早期阶段发挥作用。CD146 与年龄呈正相关,与肿瘤分期呈负相关。

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