Biological characterization and analysis of metastasis-related genes in cell lines derived from the primary lesion and lymph node metastasis of a squamous cell carcinoma arising in the mandibular gingiva
Biological characterization and analysis of metastasis-related genes in cell lines derived from the primary lesion and lymph node metastasis of a squamous cell carcinoma arising in the mandibular gingiva
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DOI：
10.3892/ijo.2014.2332
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发表时间：
2014-05-01
影响因子：
5.2
通讯作者：
Mori, Yoshihide
中科院分区：
文献类型：
--
作者：
Fujinaga, Takahiro;Kumamaru, Wataru;Mori, Yoshihide
除了控制原发病灶外，控制转移病灶是改善癌症预后的重要组成部分。已经有许多关于原发性和转移性病变的组织学研究，但是很少使用来自同一患者的原发性和转移性病变的细胞系进行基础研究。在这项研究中，我们成功地建立了一个细胞系来源于下牙龈癌（WK2），以及来自继发性颈部淋巴结转移（WK3F），通过原代培养的组织从口腔鳞状细胞癌患者。然后，我们研究了这些原发性和转移性病变的癌细胞系的生物学特性，并分析了转移相关基因。体外生物学特性比较表明，WK3F细胞增殖能力较WK2细胞高，细胞倍增时间较WK2细胞短。WK3F细胞迁移能力增强，侵袭能力和自我复制能力增强。异种移植到裸鼠中导致舌中的高肿瘤形成率和颈淋巴结中的高转移率。然后使用微阵列综合分析WK2和WK3F基因表达的变化。当Z分数>= 2.0且比率>= 5.0时，提取WK3F中与WK2相比表达增加的基因，而当Z分数>= 5.0时，提取WK3F中与WK2相比表达降低的基因。
Controlling metastatic lesions is an important part of improving cancer prognosis, in addition to controlling the primary lesion. There have been numerous histological studies on primary and metastatic lesions, but little basic research has been performed using cell lines from primary and metastatic lesions belonging to the same patient. In this study, we successfully established a cell line derived from lower gingival carcinoma (WK2) as well as a line derived from secondary cervical lymph node metastasis (WK3F) through primary cultures of tissue from a patient with oral squamous cell carcinoma. We then investigated the biological characteristics of the cancer cell lines from these primary and metastatic lesions and analyzed metastasis-related genes. Comparison of the biological characteristics in vitro showed that WK3F had higher cell proliferation ability and shorter cell doubling time than WK2. WK3F also had increased cell migratory ability and higher invasive and self-replication abilities. Heterotransplantation into nude mice resulted in high tumor formation rates in the tongue and high metastasis rates in the cervical lymph nodes. Changes in WK2 and WK3F gene expression were then comprehensively analyzed using micro-arrays. Genes with increased expression in WK3F compared to WK2 were extracted when the Z-score was >= 2.0 and the ratio was >= 5.0, while genes with reduced expression in WK3F compared to WK2 were extracted when the Z-score was