Overexpression of LAMP3/TSC403/DC-LAMP promotes metastasis in uterine cervical cancer
Overexpression of LAMP3/TSC403/DC-LAMP promotes metastasis in uterine cervical cancer
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DOI：
10.1158/0008-5472.can-04-4112
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发表时间：
2005-10-01
期刊：
影响因子：
11.2
通讯作者：
Murata, Y
中科院分区：
文献类型：
--
作者：
Kanao, H;Enomoto, T;Murata, Y
LAMP 3（DC-LAMP，TSC 403，CD 208）最初是作为在肺组织中特异性表达的基因分离的。LAMP 3位于染色体3q区段上，其在一些人类癌症（包括子宫颈癌）中经常扩增。由于溶酶体膜糖蛋白的LAMP家族的另外两个成员，LAMP 1和LAMP 2，先前涉及潜在地调节血管内皮细胞和癌细胞的相互作用，我们假设LAMP 3也可能在转移中起重要作用。为了阐明LAMP 3在宫颈癌中的转移潜力，我们将LAMP 3表达载体转染到人宫颈癌细胞系TCS中。在体外侵袭测定中，LAMP 3过表达TCS细胞的迁移显著高于对照TCS细胞。在体内转移测定中，在11只LAMP 3过表达TCS细胞注射小鼠中的9只和11只对照小鼠中的仅1只中检测到远处转移。组织学研究表明，LAMP 3过表达的细胞容易侵入淋巴管间隙。在临床样本中，定量实时逆转录-PCR（RT-PCR）分析显示，LAMP 3 mRNA在47例宫颈癌中的47例（100%）和15例宫颈上皮内瘤变中的2例（13%）中显著上调，而正常子宫颈中LAMP 3 mRNA表达水平较低。有趣的是，LAMP 3高表达与I/II期宫颈癌患者的总生存期显着相关。这些发现表明，LAMP 3过表达与增强的转移潜能相关，并且可能是宫颈癌的预后因素。
LAMP3 (DC-LAMP, TSC403, CD208) was originally isolated as a gene specifically expressed in lung tissues. LAMP3 is located on a chromosome 3q segment that is frequently amplified in some human cancers, including uterine cervical cancer. Because two other members of the LAMP family of lysosomal membrane glycoproteins, LAMP1 and LAMP2, were previously implicated in potentially modulating the interaction of vascular endothelial and cancer cells, we hypothesized that LAMP3 might also play an important part in metastasis. To clarify the metastatic potential of LAMP3 in cervical cancers, we transfected a LAMP3 expression vector into a human uterine cervical cancer cell line, TCS. In an in vitro invasion assay, the migration of LAMP3-overexpressing TCS cells was significantly higher than in control TCS cells. In an in vivo metastasis assay, distant metastasis was detected in 9 of 11 LAMP3-overexpressing TCS cell-injected mice and in only 1 of 11 control mice. Histologic study showed that LAMP3-overexpressing cells readily invaded into the lymph-vascular space. In clinical samples, quantitative real-time reverse transcription-PCR (RT-PCR) analyses showed that LAMP3 mRNA was significantly up-regulated in 47 of 47 (100%) cervical cancers and in 2 of 15 (13%) cervical intraepithelial neoplasias, compared with a low level of LAMP3 mRNA expressed in normal uterine cervixes. Interestingly, high LAMP3 expression was significantly correlated with the overall survival of patients with stage I/II cervical cancers. These findings indicate that LAMP3 overexpression is associated with an enhanced metastatic potential and may be a prognostic factor for cervical cancer.