Low dynamin 2 expression is associated with tumor invasion and metastasis in invasive squamous cell carcinoma of cervix

Low dynamin 2 expression is associated with tumor invasion and metastasis in invasive squamous cell carcinoma of cervix
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DOI:
10.4161/cbt.10.4.12275
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发表时间:
2010-08-15
影响因子:
3.6
通讯作者:
Bae, Duk-Soo
Bae, Duk-Soo
中科院分区:
医学3区
文献类型:
--
作者:
Lee, Yoo-Young;Do, In-Gu;Bae, Duk-Soo

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发动蛋白2是一种参与细胞迁移和内吞作用的蛋白质。我们的目的是研究发动蛋白2的表达和早期宫颈癌(IB 1-IIA)的肿瘤进展之间的关系。在37例石蜡包埋、福尔马林固定的组织(包括4例正常宫颈组织)中,在蛋白水平上评估发动蛋白2的表达,并与33例宫颈鳞状细胞癌患者手术后复发的病理危险因素进行比较。发动蛋白2的表达在不同临床分期和淋巴血管间隙侵犯之间无差异。然而,发动蛋白2表达与宫颈浸润深度(p = 0.003)和淋巴结(LN)转移(p = 0.001)呈负相关。为了探讨dynamin 2在肿瘤侵袭和转移中的作用机制,我们利用dynamin 2 siRNA对宫颈癌细胞系HeLa、MS 751和SiHa进行了体外实验。我们发现使用特异性siRNA抑制发动蛋白2增强了基质金属蛋白酶-2的表达。这些结果表明,发动蛋白2可能参与防止肿瘤的侵袭和淋巴结转移,可能与细胞外基质降解,并可能是这些危险因素在早期宫颈鳞状细胞癌的预后标志物。
Dynamin 2 is known as a protein involved in cell migration and endocytosis. We aimed to investigate the association between dynamin 2 expressions and tumor progression in early cervical carcinoma (IB1-IIA). Dynamin 2 expression was evaluated at protein level in thirty seven paraffin-embedded, formalin-fixed tissues including four normal cervix tissues and compared with pathologic risk factors for recurrence after surgery in thirty three patients with squamous cell carcinoma of the cervix. The expression of dynamin 2 was not different according to clinical stage and lympho-vascular space invasion. However, there were inverse correlations between dynamin 2 expression and depth of invasion in cervix (p = 0.003) and lymph node (LN) metastasis (p = 0.001). To evaluate mechanism of dynamin 2 in tumor invasion and metastasis, we performed in vitro experiment with dynamin 2 siRNA using several cervical carcinoma cell lines such as HeLa, MS751 and SiHa cells. We found the inhibition of dynamin 2 using specific siRNA enhanced the expression of matrix metalloproteinase-2. These results suggested that dynamin 2 might be involved in preventing tumor invasion and LN metastasis, possibly in relation with extracellular matrix degradation, and may be a prognostic marker for these risk factors in early squamous cell carcinoma of the cervix.