目的·探究人多效蛋白（pleiotrophin，PTN）对恶性周围神经鞘瘤（malignant peripheral nerve sheath tumor，MPNST）增殖、迁移与侵袭能力的影响。方法·通过免疫组织化学与生物信息学技术检测和分析PTN在MPNST组织中的表达。通过慢病毒转染分别构建过表达PTN与敲低PTN的MPNST细胞株，分别对过表达与敲低PTN的MPNST细胞进行细胞划痕实验与Transwell细胞迁移/侵袭实验，以检测PTN对细胞迁移、侵袭能力的影响；借助CCK8细胞增殖实验、EdU细胞增殖实验与细胞克隆形成实验，检测PTN对细胞增殖与集落形成能力的影响。通过Western blotting与转录组高通量测序技术，探究PTN对信号转导通路的影响。借助鼠尾静脉肿瘤细胞注射技术，分别注射敲减PTN的MPNST细胞株（实验组）和未敲减细胞株（对照组）构建MPNST裸鼠肺转移模型，探究PTN在体内环境下的生物学功能。结果·对49例MPNST患者的肿瘤组织与3例非MPNST患者的正常神经组织样本的免疫组织化学实验表明，PTN蛋白在MPNST组织中表达显著降低。细胞划痕实验与Transwell细胞迁移/侵袭实验显示，敲减PTN可促进MPNST细胞迁移与侵袭，过表达PTN可抑制MPNST细胞迁移与侵袭。CCK8细胞增殖实验、EdU细胞增殖实验与克隆形成实验显示：过表达PTN可抑制细胞增殖，但对集落形成能力无显著影响；敲减PTN对增殖与集落形成均无显著影响。Western blotting结果表明，过表达PTN可激活促分裂原活化的蛋白激酶（MAPK）通路，而敲减PTN对MAPK通路无显著影响。高通量转录组测序结果表明，过表达PTN可调节MPNST细胞中细胞程序性死亡的相关基因。体内实验表明，相较于对照组小鼠，实验组小鼠的成瘤率无显著改变，但生成肺转移灶的数量与体积显著上升，且出现严重的肺间质病变，实验组小鼠的体质量增长速度也显著低于对照组。结论·PTN在MPNST组织中低表达；过表达PTN可在体外抑制MPNST细胞的增殖、迁移与侵袭；敲减PTN的MPNST细胞对小鼠肺部的转移能力增强。

Objective ·To investigate the role of pleiotrophin (PTN) in the proliferation, migration and invasion of malignant peripheral nerve sheath tumor (MPNST). Methods ·The expression of PTN was verified by immunochemistry and bioinformatics analysis. By lentivirus transfection, the PTN-overexpressing and the PTN-knocked-down MPNST cell lines were established. To validate the role of PTN in MPNST migration and invasion, cell wound healing assay and Transwell migration/invasion assays were performed in boththe PTN-overexpressing MPNST cells and the PTN-knocked-down cells. By CCK8 assay, EdU assay and colony formation assay, the effects of PTN on the proliferation and the colony formation capabilities were evaluated. The pathway expression pattern regulated by PTN was validated by Western blotting and high-throughput transcriptome sequencing. To identify the biological function of PTN in vivo, an MPNST lung metastatic model in Balb/c nude mice was established. By mouse tail intravenous injection technique, PTN-knocked-down MPNST cells (experimental group) and negative control cells (control group) were injected into Balb/c nude mice, respectively. Results ·According to the immunochemistry staining results of the MPNST tissue samples from 49 patients and the normal nerve tissue samples from 3 non-MPNST people, PTN was significantly down-regulated in the MPNST tissues. In cell wound healing assay and Transwell migration/invasion assay, knocking down PTN significantly enhanced the migration and invasion capabilities of MPNST cells, while PTN overexpression inhibited them. The results of CCK8 assay, EdU assay and colony formation assay indicated that PTN overexpression hindered the proliferation of MPNST cells while colony formation was barely impacted; no significant differences in these assays were detected in the PTN-knocked-down cells. According to Western blotting assay, PTN overexpression activated mitogen activated protein kinase (MAPK) pathway while knocking down PTN showed mild influence. Transcriptome high-throughput sequencing showed that the expression levels of the genes related with programmed cell death pathway changed in the PTN-overexpressing cells. In the in vivo experiments, there was no significant difference in the tumor formation rate; however, the quantity and the volume of lung metastasis lesions were both larger in the experimental group. The most mice in the experimental group were diagnosed with severe pulmonary interstitial disease, and their growth rate of body mass also decreased. Conclusion ·PTN is down-regulated in the MPNST tissue and overexpressing PTN inhibites proliferation, migration and invasion of the MPNST cells in vitro. The ability of PTN-knocked-down MPNST cells to metastasize to the lungs in mice is enhanced.