Overexpression of LAMP3/TSC403/DC-LAMP promotes metastasis in uterine cervical cancer

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。由于其他两个成员的LAMP家族的溶酶体膜糖蛋白，LAMP 1和LAMP 2，以前被牵连在潜在的调节血管内皮细胞和癌细胞的相互作用，我们假设，LAMP 3也可能发挥重要的作用，在metastasis.To澄清的转移潜力的LAMP 3在宫颈癌，我们转染的LAMP 3表达载体到人子宫颈癌细胞系，TCS。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。实时荧光定量RT-PCR检测结果显示，在47例宫颈癌和15例宫颈上皮内瘤变（CIN）中，LAMP 3 mRNA表达明显上调（分别为47例（100%）和2例（13%），而正常宫颈组织中LAMP 3 mRNA表达水平较低。有趣的是，LAMP 3高表达与I/II期宫颈癌患者的总体生存率显著相关，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 the 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. Histological study showed that LAMP3-overexpressing cells readily invaded into the lymph-vascular space.In clinical samples, quantitative real-time 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 (CINs), compared to 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.