Document Detail


Dentin sialophosphoprotein (DSPP) gene-silencing inhibits key tumorigenic activities in human oral cancer cell line, OSC2.
MedLine Citation:
PMID:  21103065     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: We determined recently that dentin sialophosphoprotein (DSPP), a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins, is highly upregulated in human oral squamous cell carcinomas (OSCCs) where upregulation is associated with tumor aggressiveness. To investigate the effects of DSPP-silencing on the tumorigenic profiles of the oral cancer cell line, OSC2, short-hairpin RNA (shRNA) interference was employed to silence DSPP in OSC2 cells.
METHODOLOGY/PRINCIPAL FINDINGS: Multiple regions of DSPP transcript were targeted for shRNA interference using hDSP-shRNA lentiviral particles designed to silence DSPP gene expression. Control shRNA plasmid encoding a scrambled sequence incapable of degrading any known cellular mRNA was used for negative control. Following puromycin selection of stable lines of DSSP-silenced OSC2 cells, phenotypic hallmarks of oral carcinogenesis were assayed by western blot and RT-PCR analyses, MTT (cell-viability), colony-formation, modified Boyden-Chamber (migration and invasion), and flow cytometry (cell-cycle and apoptosis) analyses. DSPP-silenced OSC2 cells showed altered cell morphology, reduced viability, decreased colony-formation ability, decreased migration and invasion, G0/G1 cell-cycle arrest, and increased tumor cell sensitivity to cisplatin-induced apoptosis. Furthermore, MMP-2, MMP-3, MMP-9, VEGF, Ki-67, p53, and EGFR were down-regulated. There was a direct correlation between the degree of DSPP-silencing and MMP suppression, as indicated by least squares regression: MMP-2 {(y = 0.850x, p<0.001) (y = 1.156x, p<0.001)}, MMP-3 {(y = 0.994x, p<0.001) (y = 1.324x, p = 0.004)}, and MMP-9 {(y = 1.248x, p = 0.005, y = 0.809, p = 0.013)}.
CONCLUSIONS/SIGNIFICANCE: DSPP-silencing in OSC2 cell decreased salient hallmarks of oral tumorigenesis and provides the first functional evidence of a potential key role for DSPP in oral cancer biology. The down-regulation of MMP-2, MMP-3, MMP-9, p53 and VEGF in DSPP-silenced OSC2 cells provides a significant functional/molecular framework for deciphering the mechanisms of DSPP activities in oral cancer biology.
Authors:
Rajeshree Joshi; Amany Tawfik; Nneka Edeh; Veronica McCloud; Stephen Looney; Jill Lewis; Stephen Hsu; Kalu U E Ogbureke
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-12
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-04-27     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e13974     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology
Apoptosis / drug effects
Blotting, Western
Cell Line
Cell Line, Tumor
Cell Movement
Cisplatin / pharmacology
Extracellular Matrix Proteins / genetics*,  metabolism
Female
Humans
Keratinocytes / cytology,  metabolism
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 3 / metabolism
Matrix Metalloproteinase 9 / metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
Mouth Neoplasms / genetics*,  pathology
Neoplasms, Experimental / genetics,  pathology
Phosphoproteins / genetics*,  metabolism
RNA Interference*
Reverse Transcriptase Polymerase Chain Reaction
Sialoglycoproteins / genetics*,  metabolism
Transplantation, Heterologous
Tumor Suppressor Protein p53 / metabolism
Up-Regulation*
Grant Support
ID/Acronym/Agency:
K23 DE017791/DE/NIDCR NIH HHS; K23 DE017791-05/DE/NIDCR NIH HHS; K23DE017791-01A1/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Extracellular Matrix Proteins; 0/Phosphoproteins; 0/Sialoglycoproteins; 0/Tumor Suppressor Protein p53; 0/dentin sialophosphoprotein; EC 3.4.24.17/Matrix Metalloproteinase 3; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9; Q20Q21Q62J/Cisplatin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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