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Suppression of invasive properties of colorectal carcinoma SW480 cells by 15-hydroxyprostaglandin dehydrogenase gene
Li M.1; Xie J.1; Cheng L.2; Chang B.1; Wang Y.1; Lan X.1; Zhang D.1; Yin Y.1; Cheng N.1
2008-11-01
Source PublicationCancer Investigation
ISSN07357907 15324192
Volume26Issue:9Pages:905-912
AbstractColorectal carcinoma (CRC) is often lethal when invasion and/or metastasis occur. NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme involved in prostaglandin (including PGE2) bio-inactivation, is down-expressed in several epithelial malignancies including CRC. Although its role in the suppression of colon tumorigenesis has been well learned, little is known about the role of 15-PGDH in the process of tumor metastasis. Here, we tested the hypothesis that 15-PGDH over-expression in CRC cells results in decreased cell motility and invasion. In this study, 15-PGDH was re-expressed in SW480 cells by the use of gene transient transfection with eukaryotic expression vector pcDNA3.1-PGDH. We confirmed the over-expression of 15-PGDH protein by Western blot and enzymatic activity assay. The cell motility was tested by counting the number of cells crossing an 8-micron pore size PET membrane and by measuring cells migration distance through wound healing assay. Furthermore, cell invasive activity was evaluated by counting the number of cells invading through a Matrigel-coated membrane simulating basement membrane. The effects of 15-PGDH on the adhesion were investigated by MTT assay. Ectopic expression of 15-PGDH in SW480 cancer cells significantly inhibited the cell migratory and invasive capacity in vitro by approximately 1.9- and 8.4-fold, respectively. To test the hypothesis that 15-PGDH affects proteases and inactivates extracellular matrix (ECM), Western blot and gelatin zymography were performed by using serum-free conditioned medium. The results showed that re-expression of 15-PGDH suppresed matrix metalloproteinase-2 (MMP2) synthesis and secretion. In addition, the analysis of the MMP2 activity indicated that re-expression of 15-PGDH could inhibit activation of MMP2. Furthermore, we found that 15-PGDH inhibited cell adhesion to ECM and reduced CD44 expression in SW480 cell. Taken together, these results suggest that induced 15-PGDH expression may contribute to the inhibition of the invasive and metastatic capacity of colon cancer cells in vitro. Copyright © Informa Healthcare USA, Inc.
Keyword15-PGDH Colorectal carcinoma Metastasis MMP2
DOI10.1080/07357900802146154
URLView the original
Language英語
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Cited Times [WOS]:14   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Shanxi Medical University
2.Cornell University
Recommended Citation
GB/T 7714
Li M.,Xie J.,Cheng L.,et al. Suppression of invasive properties of colorectal carcinoma SW480 cells by 15-hydroxyprostaglandin dehydrogenase gene[J]. Cancer Investigation,2008,26(9):905-912.
APA Li M..,Xie J..,Cheng L..,Chang B..,Wang Y..,...&Cheng N..(2008).Suppression of invasive properties of colorectal carcinoma SW480 cells by 15-hydroxyprostaglandin dehydrogenase gene.Cancer Investigation,26(9),905-912.
MLA Li M.,et al."Suppression of invasive properties of colorectal carcinoma SW480 cells by 15-hydroxyprostaglandin dehydrogenase gene".Cancer Investigation 26.9(2008):905-912.
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