Document Detail


Increased invasive potential and up-regulation of MMP-2 in MDA-MB-231 breast cancer cells expressing the beta3 integrin subunit.
MedLine Citation:
PMID:  17203213     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Integrins are a family of transmembrane adhesion receptors that might transduce signals from the extracellular matrix into the inside of cells after ligand binding. In order to investigate whether beta3 integrins expressed in tumor cells might mediate such outside-in signaling, human MDA-MB-231 breast cancer cells that were stably transfected with either beta3 integrin or mock-transfected were investigated in a matrigel degradation assay and a grafting experiment was performed on the developing chicken chorioallantoic membrane (CAM). After cultivation on matrigel for time periods between one and five days, more matrigel was digested in the wells in which beta3 integrin expressing cells were incubated than in wells of mock-transfected cells. Furthermore, extracts of beta3 integrin expressing cells contained higher levels of MMP-2 protein as determined by immunoblotting and more MMP-2 associated gelatinase activity as detected by zymography than extracts of mock-transfected cells. Matrigel degradation and gelatinase activity as well as MMP-2 expression were elevated when beta3 integrin expressing cells were incubated in the presence of the RGD peptide (mimicking an integrin ligand). After grafting on 10 day-old embryonic chicken CAM for three to five days, beta3 integrin expressing cells assembled in spheroids showed higher rates of spreading on the CAM surface and CAM invasion as well as a significant MMP-2 up-regulation compared to mock-transfected cells. The results from the in vivo and in vitro experiments allow the conclusion that the presence of beta3 integrin in MDA-MB-231 breast cancer cells induced an increased MMP-2 expression and activity that might contribute to the enhanced invasive potential observed.
Authors:
Oliver Baum; Ruslan Hlushchuk; Andrea Forster; Richard Greiner; Philipp Clézardin; Yingshe Zhao; Valentin Djonov; Günther Gruber
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  30     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-04     Completed Date:  2007-04-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  325-32     Citation Subset:  IM    
Affiliation:
Institute of Anatomy, University of Bern, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Breast Neoplasms / metabolism*
Cell Line, Tumor
Chickens
Collagen / chemistry
Drug Combinations
Gene Expression Regulation, Neoplastic*
Humans
Integrin beta3 / biosynthesis*
Laminin / chemistry
Ligands
Matrix Metalloproteinase 2 / biosynthesis*
Neoplasm Invasiveness
Proteoglycans / chemistry
Time Factors
Transfection
Up-Regulation*
Chemical
Reg. No./Substance:
0/Drug Combinations; 0/Integrin beta3; 0/Laminin; 0/Ligands; 0/Proteoglycans; 119978-18-6/matrigel; 9007-34-5/Collagen; EC 3.4.24.24/Matrix Metalloproteinase 2

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


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