Document Detail


VEGFR and EGFR inhibition increases epithelial cellular characteristics and chemotherapy sensitivity in mesenchymal bladder cancer cells.
MedLine Citation:
PMID:  20811684     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The present study investigated the effect of VEGFR and EGFR inhibition via vandetanib (Zactima) on epithelial-mesenchymal transition (EMT) in bladder cancer. Markers of EMT (EGFR, VEGR, E-cadherin and vimentin) were interogated by Western blotting at baseline and after treatment with EGF, VEGF, vandetanib, cisplatin, or their combination using representative epithelial- and mesenchymal-type human bladder cancer cells. Morphological changes induced by these treatments were examined by microscopy over various time courses. The effect of these changes on cisplatin chemotherapy sensitivity was assessed by MTT assay. RT4 and HTB3 cells had epithelial features while CRL1749 and J82 cells had mesenchymal features. After treatment with EGF, the epithelial-type cells demonstrated increased intercellular separation and pseudopodia, with these changes blocked by vandetanib. In contrast, the mesenchymal cells did not exhibit any morphological changes with the EGF treatment but adopted a clustered/epithelial appearance after the administration of vandetanib. Western blotting shows that treatment of epithelial cells with vandetanib increased the expression of E-cadherin. In comparison, mesenchymal cells demonstrated decreased vimentin expression with the treatment of vandetanib in the presence of EGF and VEGF. Improved growth inhibition was seen in the epithelial cells but not in mesenchymal cells with the concurrent treatment of vandetanib and cisplatin. Sequential treatment of mesenchymal cells with vandetanib followed by cisplatin demonstrated synergy with improved cisplatin activity. The findings offer a novel role of vandetanib on the EMT in bladder cancer, providing insight into EMT in bladder cancer.
Authors:
Yuan Li; Xiaoping Yang; Lih-Jen Su; Thomas W Flaig
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Oncology reports     Volume:  24     ISSN:  1791-2431     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-02     Completed Date:  2011-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1019-28     Citation Subset:  IM    
Affiliation:
Division of Medical Oncology, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Blotting, Western
Cadherins / biosynthesis
Cell Line, Tumor
Cisplatin / pharmacology
Drug Resistance, Neoplasm / physiology
Epithelial Cells / drug effects,  metabolism
Epithelial-Mesenchymal Transition / drug effects*,  physiology
Humans
Mesoderm / pathology
Piperidines / pharmacology
Quinazolines / pharmacology
Receptors, Vascular Endothelial Growth Factor / metabolism*
Urinary Bladder Neoplasms / metabolism,  pathology*
Vimentin / biosynthesis
Grant Support
ID/Acronym/Agency:
K12CA086913/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Cadherins; 0/N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine; 0/Piperidines; 0/Quinazolines; 0/Vimentin; 15663-27-1/Cisplatin; EC 2.7.10.1/Receptors, Vascular Endothelial Growth Factor

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


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