Upregulation of SPOCK2 inhibits the invasion and migration of prostate cancer cells by regulating the MT1-MMP/MMP2 pathway.

Gang Liu,Yongsheng Song,Fang Ren

doi:10.7717/peerj.7163

Abstract

BackgroundIt is known that secreted protein acidic and cysteine rich (osteonectin), cwcv and kazal-like domains proteoglycan 2 (SPOCK2) plays a significant role in the development and progression of several human cancers; however, the role of SPOCK2 in prostate cancer (PCa) remains unclear. This study aimed to find the role and mechanism of SPOCK2 in the development and progression of PCa.MethodsThe messenger ribonucleic acid (mRNA) expression of SPOCK2 in PCa tissue was detected by real-time polymerase chain reaction (PCR). Upregulation of the SPOCK2 gene was achieved using the DU145 and LNCaP cells by transfecting the cells with SPOCK2 recombinant fragment. Cell invasion and migration ability were detected by transwell chamber and wound healing assay. The expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase 2 (MMP2) in the cells was detected by Western Blot and zymography gel assay.ResultsThe mRNA level of SPOCK2 was significantly lower in the PCa tissue compared to benign prostate hyperplasia. Upregulation of SPOCK2 inhibited cell invasion and migration in DU145 and LNCaP cells, inhibited the expression of MT1-MMP and MMP2 and, inhibited activation of MMP2 in DU145 and LNCaP cells.ConclusionSPOCK2 is associated with the progression of PCa. Upregulation of SPOCK2 can inhibit PCa cell invasion and metastasis by decreasing MT1-MMP and MMP2 gene expression and decreasing MMP2 protein activation.

Highlights

Prostate cancer (PCa) is the most common cancer diagnosed among men in developed countries, and it has become the most common malignant tumor of the urinary system and the fastest growing male malignancy in China (Zheng et al, 2016; Chen et al, 2015; Chen et al, 2016b)
SPOCK2 messenger ribonucleic acid (mRNA) expression in tissue There was no significant difference between the age of the prostate cancer (PCa) group (69.27 ± 9.15) and the benign prostate hyperplasia (BPH) group (66.97 ± 5.95) (P > 0.05)
SPOCK2 gene expression after transfection The recombinant SPOCK2 fragment was transfected into the DU145 and LNCaP cells by adenovirus, and the SPOCK2 mRNA level and protein expression in the cells after transfection detected by real-time polymerase chain reaction (PCR) (Fig. 1) and Western Blot (WB) (Fig. 2), respectively

Summary

Introduction

Prostate cancer (PCa) is the most common cancer diagnosed among men in developed countries, and it has become the most common malignant tumor of the urinary system and the fastest growing male malignancy in China (Zheng et al, 2016; Chen et al, 2015; Chen et al, 2016b). Upregulation of SPOCK2 inhibits the invasion and migration of prostate cancer cells by regulating the MT1-MMP/MMP2 pathway. Studying the mechanism of invasion and metastasis of PCa is of great significance for improving the prognosis of PCa. It is known that secreted protein acidic and cysteine rich (osteonectin), cwcv and kazal-like domains proteoglycan 2 (SPOCK2) plays a significant role in the development and progression of several human cancers; the role of SPOCK2 in prostate cancer (PCa) remains unclear. This study aimed to find the role and mechanism of SPOCK2 in the development and progression of PCa. Methods: The messenger ribonucleic acid (mRNA) expression of SPOCK2 in PCa tissue was detected by real-time polymerase chain reaction (PCR). Conclusion: SPOCK2 is associated with the progression of PCa. Upregulation of SPOCK2 can inhibit PCa cell invasion and metastasis by decreasing MT1-MMP and MMP2 gene expression and decreasing MMP2 protein activation

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