Document Detail


Stanniocalcin-2 promotes epithelial-mesenchymal transition and invasiveness in hypoxic human ovarian cancer cells.
MedLine Citation:
PMID:  20619259     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The human glycoprotein, stanniocalcin-2 (STC2) is a HIF-1 target gene that is found to be associated with tumor development. The relationship of the prognostic outcome to the level of its expression in cancer tissues is controversial; however experimental evidence suggests that STC2 is a positive regulator of cancer progression. In the present study, we investigated if the expression of STC2 in hypoxic cells is associated with cancer invasion and metastasis. We studied the epithelial-mesenchymal transition (EMT) markers in STC2-silenced and over-expressed SKOV3 cells maintained in hypoxic condition. Western blot and immunocytochemical analysis revealed that the stable expression of exogenous STC2 promoted EMT, as revealed by the increase of N-cadherin/vimentin but a decrease of E-cadherin levels. This observation was further confirmed by colony formation assay where the STC2 stably transfected cells showed high degree of motility with fibroblast morphology under hypoxic condition. In conducting invasion assay in hypoxia, the STC2 stably transfected cells showed high degree of invasiveness. This observation was correlated with the significant increase of MMP2 and MMP9 expression in the STC2 stably transfected cells. In HUVEC/SKOV3 co-culture invasion study, endothelial invasion was found to be enhanced by the seeding of STC2 stably transfected cells in the lower compartment. These observations were possibly mediated by an increase of ROS and activated ERK1/2 levels in the cells. Collectively, the finding provides the first evidence that STC2 is a positive regulator in tumor progression at hypoxia.
Authors:
Alice Y S Law; Chris K C Wong
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-07
Journal Detail:
Title:  Experimental cell research     Volume:  316     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-09     Completed Date:  2011-01-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3425-34     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD / metabolism
Cadherins / metabolism
Cell Hypoxia / physiology*
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation
Coculture Techniques
Endothelial Cells / cytology
Epithelial-Mesenchymal Transition* / genetics
Female
Gene Expression / genetics
Glycoproteins / genetics,  metabolism*
Humans
Intercellular Signaling Peptides and Proteins / genetics,  metabolism*
Matrix Metalloproteinase 2 / genetics,  metabolism
Matrix Metalloproteinase 9 / genetics,  metabolism
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Neoplasm Invasiveness* / genetics
Neovascularization, Pathologic / genetics
Ovarian Neoplasms / genetics,  metabolism*,  pathology*
Phosphorylation
RNA, Small Interfering / genetics
Reactive Oxygen Species / metabolism
Transcription Factors / metabolism
Transfection
Vimentin / metabolism
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/CDH2 protein, human; 0/Cadherins; 0/Glycoproteins; 0/Intercellular Signaling Peptides and Proteins; 0/RNA, Small Interfering; 0/Reactive Oxygen Species; 0/STC2 protein, human; 0/Transcription Factors; 0/Vimentin; 0/snail family transcription factors; EC 2.7.11.24/MAPK1 protein, human; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9

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