Preferentially Expressed Antigen of Melanoma Prevents Lung Cancer Metastasis.

Quan Huang,Shuai Han,Wei Xu,Lei Li,Xinghai Yang,Wenjiao Cao,Zaijun Lin,Yunfei Xu,Zhipeng Wu,Zhengwang Sun,Liangfang Yao,Dianwen Song,Haifeng Wei,Lin Li,Jianru Xiao,Aamir Ahmad

doi:10.1371/journal.pone.0149640

Abstract

Lung cancer is the most common cause of cancer death worldwide. The poor survival rate is largely due to the extensive local invasion and metastasis. However, the mechanisms underlying the invasion and metastasis of lung cancer cells remain largely elusive. In this study, we examined the role of preferentially expressed antigen of melanoma (PRAME) in lung cancer metastasis. Our results show that PRAME is downregulated in lung adenocarcinoma and lung bone metastasis compared with normal human lung. Knockdown of PRAME decreases the expression of E-Cadherin and promotes the proliferation, invasion, and metastasis of lung cancer cells by regulating multiple critical genes, most of which are related to cell migration, including MMP1, CCL2, CTGF, and PLAU. Clinical data analysis reveals that the expression of MMP1 correlates with the clinical features and outcome of lung adenocarcinoma. Taken together, our data demonstrate that PRAME plays a role in preventing the invasion and metastasis of lung adenocarcinoma and novel diagnostic or therapeutic strategies can be developed by targeting PRAME.

Highlights

Lung cancer is the leading cause of cancer-related mortality in the world
To investigate the role of preferentially expressed antigen of melanoma (PRAME) in lung cancer cell progression, we examined the effect of PRAME knockdown on lung cancer cell proliferation and invasion
To translate the above in vitro results into clinical studies, we examined the expression of both PRAME and E-cadherin in normal human lung tissue, human lung adenocarcinoma, and lung bone metastasis

Summary

Introduction

Lung cancer is the leading cause of cancer-related mortality in the world. About 220,000 new cases and 160,000 deaths from lung cancer were reported in the United States in 2014 [1]. Lung adenocarcinoma, belonging to non-small cell lung cancer (NSCLC), is the most common type of lung cancer accounting for more than 50% of NSCLC. Lung adenocarcinoma has an extremely poor prognosis once it has progressed to the metastatic stage. The 5-year relative survival rate for those diagnosed with lung cancer that has metastatic tumors is about 2%, far less than those without metastasis. Development of novel strategies for the prevention of metastasis helps people to live longer and increase their quality of life

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Results

Conclusion