Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
Division of Thoracic Surgery, Department of Surgery, Milton S. Hershey Medical Center, Mail Code H149, P. O. Box 850, Hershey, PA, 17033, USA.
Clin Exp Metastasis. 2018 Feb;35(1-2):15-23. doi: 10.1007/s10585-017-9869-3. Epub 2017 Dec 7.
Metastasis suppressor 1 (MTSS1) has been shown to be a metastasis suppressor in a number of cancers. However, its role in lung adenocarcinoma is largely unknown. To evaluate the significance of MTSS1 expression on lung adenocarcinoma metastatic properties, the gain or loss of MTSS1 in in vivo and in vitro experiments were employed. Using an in vivo orthotopic mouse xenograft model mimicking human disease progression, stable overexpression of MTSS1 in lung adenocarcinoma cells resulted in a significant decrease in metastatic burden. Stable overexpression of MTSS1 in NCI-H1299 decreased in vitro lung adenocarcinoma invasion and migration while knockdown of MTSS1 in A549 resulted in a significant increase in cell invasion and migration. Using The Cancer Genome Atlas dataset of over 500 patient lung adenocarcinoma specimens, we demonstrated a 20% increase in 5-year survival associated with preserved intratumoral MTSS expression. MTSS1 expression in lung adenocarcinoma is associated with decreased metastatic burden, as assessed by an in vivo orthotopic model, and correlates with a 20% survival advantage at 5 years following diagnosis. In vitro data suggests MTSS1 regulates lung adenocarcinoma through augmentation of cell invasion and migration.
转移抑制因子 1（MTSS1）在许多癌症中被证实为转移抑制因子。然而，其在肺腺癌中的作用在很大程度上尚不清楚。为了评估 MTSS1 表达对肺腺癌转移特性的意义，我们在体内和体外实验中分别采用了过表达和敲低 MTSS1 的方法。利用模拟人类疾病进展的体内原位小鼠异种移植模型，肺腺癌细胞中 MTSS1 的稳定过表达导致转移负担显著降低。NCI-H1299 中 MTSS1 的稳定过表达降低了体外肺腺癌细胞的侵袭和迁移能力，而 A549 中 MTSS1 的敲低则导致细胞侵袭和迁移能力显著增加。通过对超过 500 例患者肺腺癌标本的癌症基因组图谱数据集的分析，我们发现与肿瘤内 MTSS 表达保留相关的 5 年生存率增加了 20%。在体内原位模型中评估，肺腺癌中 MTSS1 的表达与转移负担降低相关，并且在诊断后 5 年的生存率提高了 20%。体外数据表明，MTSS1 通过增强细胞侵袭和迁移来调节肺腺癌。
