Impact of pigment epithelium-derived factor on colorectal cancer in vitro and in vivo.

Rhiannon L Harries,Sioned Owen,Jun Cai,Meleri Morgan,Fiona Ruge,Jun Li,Wen G Jiang,Jared Torkington,Zhangtao Zhang,Keith G Harding

doi:10.18632/oncotarget.24953

Abstract

Pigment epithelial derived factor (PEDF) is a secreted glycoprotein that is a non-inhibitory member of the serine protease inhibitor (serpin) family. PEDF exhibits multiple biological properties including neuroprotective, anti-angiogenic, and immune-modulating. Interestingly, PEDF exerts the inhibitory effects in cancers derived from certain tissues, including prostatic, ovarian, and pancreatic carcinomas. The current study aimed to elucidate its role in colorectal cancer development. PEDF expression in human colorectal cancer tissue was assessed using quantitative polymerase chain reaction (qPCR) and immunohistochemical staining (IHC). The effect of treatment with recombinant PEDF on cellular function was examined using in vitro functional assays. PEDF expression was downregulated in colorectal cancer cell tissue. Treatment with recombinant PEDF resulted in significant decreases in the rate of colorectal cancer cell migration and invasion and an increase in cellular adhesion in colorectal cancer cell lines examined. These results indicate that upregulation of PEDF expression may serve as a new strategy for further investigation of therapeutic relevance to the prevention of the metastatic spread of colorectal cancer.

Highlights

Pigment epithelium-derived factor (PEDF), known as early population double level complementary deoxyribonucleic acid (cDNA)-1 (EPC1), is a 50 kDa secreted glycoprotein
Expression screening for Pigment epithelial derived factor (PEDF) was performed using both colorectal cancer tissue samples obtained from the clinical cohort and colorectal cancer cell lines
The results of this study demonstrate that PEDF messenger ribonucleic acid (RNA) (mRNA) expression was lower in colorectal cancer cell lines when compared to normal colorectal fibroblasts and in colorectal cancer tissue compared to normal tissue

Summary

Introduction

Pigment epithelium-derived factor (PEDF), known as early population double level cDNA-1 (EPC1), is a 50 kDa secreted glycoprotein. It was first identified when Tombran-Tink’s group were studying human retinal cell development. They found a factor that was secreted by the human foetal retinal pigment epithelial cells and showed it to be a potent neurite promoting factor [1]. PEDF was found to be a member of the non-inhibitory serpin gene family [2]. The gene encoding PEDF (SERPINF1) is localised to the chromosome 17p13.1 [3]. There is evidence that PEDF is pleiotropic with multiple biological properties including neuroprotective, anti-tumorigenic and immune-modulating [4,5] and has been shown to be one of the most potent endogenous inhibitors of angiogenesis, more so than angiostatin, endostatin, and thrombospondin-1 [6,7]

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Conclusion