CEACAM1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases
CEACAM1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases
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DOI：
10.1038/sj.onc.1210077
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发表时间：
2007-04-26
期刊：
影响因子：
8
通讯作者：
Asa, S. L.
中科院分区：
文献类型：
--
作者：
Liu, W.;Wei, W.;Asa, S. L.
CEACAM1又称胆汁糖蛋白(BGP)、CD66a、pp120和C-CAM1，是CEA免疫球蛋白超家族的成员。CEACAM1是一种可能的肿瘤抑制因子，其基础是在某些实体肿瘤如结直肠癌中表达减弱。然而，CEACAM1在一些肿瘤中过表达，如非小细胞肺癌。为了阐明这种细胞黏附分子的作用机制，我们研究了甲状腺癌，它具有一系列的形态和不同的行为，允许将增殖与侵袭和转移分开。CEACAM1在甲状腺癌细胞系中表达，这些细胞系来自表现出侵袭性行为的肿瘤。将CEACAM1引入内源性缺陷的WRO细胞，导致与p21上调相关的细胞周期进程减少，并减少Rb的磷酸化。强制表达CEACAM1增强了细胞-基质的黏附和迁移，促进了肿瘤的侵袭。相反，小干扰RNA(SiRNA)介导的CEACAM1表达下调在MRO细胞中加速了细胞周期进程，并显著增加了异种移植小鼠的肿瘤大小。CEACAM1在正常甲状腺组织和良性甲状腺肿瘤中不表达。在人类甲状腺组织阵列中，CEACAM1的反应性与转移扩散有关，但与肿瘤大小增加无关。这些发现确认CEACAM1是一种独特的介质，它限制了肿瘤的生长，但增加了转移潜力。我们的数据突出了一系列复杂的作用，为甲状腺癌相关的生物学行为谱提供了可能的机制。
CEACAM1, also known as biliary glycoprotein (BGP), CD66a, pp120 and C-CAM1, is a member of the CEA immunoglobulin superfamily. CEACAM1 is a putative tumor suppressor based on diminished expression in some solid neoplasms such as colorectal carcinoma. However, CEACAM1 is overexpressed in some tumors such as non-small cell lung cancer. To clarify the mechanism of action of this cell adhesion molecule, we studied thyroid carcinoma that has a spectrum of morphologies and variable behavior allowing separation of proliferation from invasion and metastasis. CEACAM1 is expressed in thyroid carcinoma cell lines derived from tumors that exhibit aggressive behavior. Introduction of CEACAM1 into endogenously deficient WRO cells resulted in reduced cell cycle progression associated with p21 upregulation and diminished Rb phosphorylation. Forced CEACAM1 expression enhanced cell-matrix adhesion and migration and promoted tumor invasiveness. Conversely, small interfering RNA (siRNA)-mediated downregulation of CEACAM1 expression in MRO cells accelerated cell cycle progression and significantly enhanced tumor size in xenografted mice. CEACAM1 is not appreciably expressed in normal thyroid tissue or benign thyroid tumors. In a human thyroid tissue array, CEACAM1 reactivity was associated with metastatic spread but not with increased tumor size. These findings identify CEACAM1 as a unique mediator that restricts tumor growth whereas increasing metastatic potential. Our data highlight a complex repertoire of actions providing a putative mechanism underlying the spectrum of biologic behaviors associated with thyroid cancer.