EFEMP1 promotes the migration and invasion of osteosarcoma via MMP-2 with induction by AEG-1 via NF-κB signaling pathway.

Zhuo Wang,Zhong-Wei Lin,Chuang-Jie Cao,Lian-Tang Wang,Lei-Lei Huang,Zun-Fu Ke,Fen Wang,Yuan-Qi Zhang,Can-Jiao Luo

doi:10.18632/oncotarget.3691

Abstract

The role of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) in osteosarcoma remains unknown. Then applying EFEMP1 siRNA, plasmids transfection and adding purified EFEMP1 protein in human osteosarcoma cell lines, and using immunohistochemistry on 113 osteosarcoma tissues, demonstrated that EFEMP1 was a poor prognostic indicator of osteosarcoma; EFEMP1 was specifically upregulated in osteosarcoma and associated with invasion and metastasis in vitro and in vivo. At the same time, we found a direct regulatory effect of EFEMP1 on MMP-2. Moreover, we firstly found the marked induction of EFEMP1 by oncogenic AEG-1. And EFEMP1 expression was inhibited by the selective inhibitor of NF-κB (PDTC) in osteosarcoma cells. Then we thought that NF-κB pathways might be one of the effective ways which EFEMP1 was induced by AEG-1. Thus, we suggested that EFEMP1 played a part as the mediator between AEG-1 and MMP-2. And NF-κB signaling pathway played an important role in this process. In summary, EFEMP1 was associated with invasion, metastasis and poor prognosis of osteosarcoma patients. EFEMP1 might indirectly enhance the expression of MMP-2, providing a potential explanation for the role of AEG-1 in metastasis. NF-κB pathways might be one of the effective ways which EFEMP1 was induced by AEG-1.

Highlights

Osteosarcoma is the most common primary malignant tumor of the bone in children and adolescents with a poor prognosis
We thought that nuclear factor-κB (NF-κB) pathways might be one of the effective ways which EFEMP1 was induced by astrocyte elevated gene-1 (AEG-1)
To further investigate whether EFEMP1 was overexpressing in clinical samples of osteosarcoma, immunohistochemistry, western blotting and qRT-polymerase chain reaction (PCR) analyses were used to evaluate the expression of EFEMP1 at both protein and mRNA levels

Summary

Introduction

Osteosarcoma is the most common primary malignant tumor of the bone in children and adolescents with a poor prognosis. The etiology and progression events intrinsic to the malignant properties of osteosarcoma remain obscure. Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1), called fibulin-3, is a member of the fibulin family of extracellular glycoproteins which distributed in various human tissues [1]. They modulate the cell morphology, growth, adhesion, and motility, etc [1]. EFEMP1 was associated with inherited forms of macular degeneration [3]

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