Suppression of invasion and metastasis in aggressive salivary cancer cells through targeted inhibition of ID1 gene expression.
Suppression of invasion and metastasis in aggressive salivary cancer cells through targeted inhibition of ID1 gene expression.
复制标题
DOI：
10.1016/j.canlet.2016.04.021
复制
发表时间：
2016-07-10
期刊：
影响因子：
9.7
通讯作者：
Desprez PY
中科院分区：
文献类型：
--
作者：
Murase R;Sumida T;Kawamura R;Onishi-Ishikawa A;Hamakawa H;McAllister SD;Desprez PY
唾液腺癌（SGC）是头颈部最常见的恶性肿瘤，经常转移到肺部。螺旋-环-螺旋ID1蛋白已被证明控制许多类型癌症的转移进展。使用两种不同的方法来靶向ID1的表达（基因敲低和黄体酮受体导入联合黄体酮治疗），我们之前确定了唾液腺肿瘤ACCM细胞在培养中的侵袭性被抑制。在这里，我们使用相同的方法靶向ID1表达，研究了ACCM细胞在裸鼠中产生肺转移灶的能力。此外，由于这两种方法在人类身上的应用都具有挑战性，我们增加了第三种方法，即用一种无毒的大麻素化合物治疗小鼠，这种化合物可以下调ID1基因的表达。所有针对促转移性ID1基因的方法都能显著减少肺转移灶的形成。因此，在动物模型中，使用不同的方法靶向一个关键的转录调节因子可以相同地减少SGC细胞的转移扩散，这为治疗侵袭性SGC患者提供了一种新的方法。
Salivary gland cancer (SGC) represents the most common malignancy in the head and neck region, and often metastasizes to the lungs. The helix–loop–helix ID1 protein has been shown to control metastatic progression in many types of cancers. Using two different approaches to target the expression of ID1 (genetic knockdown and progesterone receptor introduction combined with progesterone treatment), we previously determined that the aggressiveness of salivary gland tumor ACCM cells in culture was suppressed. Here, using the same approaches to target ID1 expression, we investigated the ability of ACCM cells to generate lung metastatic foci in nude mice. Moreover, since both approaches would be challenging for applications in humans, we added a third approach, i.e., treatment of mice with a non-toxic cannabinoid compound known to down-regulate ID1 gene expression. All approaches aimed at targeting the pro-metastatic ID1 gene led to a significant reduction in the formation of lung metastatic foci. Therefore, targeting a key transcriptional regulator using different means results in the same reduction of the metastatic spread of SGC cells in animal models, suggesting a novel approach for the treatment of patients with aggressive SGC.