Linked Life Data

14648659

Source:http://linkedlifedata.com/resource/pubmed/id/14648659

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-12-3
pubmed:abstractText
In normal breast and ductal carcinoma in situ, myoepithelial cells form an incomplete layer separating the epithelial compartment from the stromal environment. Transition to invasive disease is marked by penetration of the myoepithelial-basement membrane (BM) interface. One mechanism involved in tumour invasion is breakdown of extracellular matrices by matrix metalloproteinases (MMPs). It was hypothesized that myoepithelial cells may modulate tumour invasion by controlling MMP gene expression, both in tumour cells and in peri-ductal fibroblasts. To investigate this, myoepithelial cells from normal breast were purified and characterized and their effect on tumour cell invasive potential was assessed. The effect on MMP gene expression of breast cancer cells cultured alone or in combination with primary normal breast fibroblasts was also analysed using RT-PCR with ELISA quantitation, with zymographic analysis to measure enzyme activity. Normal breast myoepithelial cells significantly reduced invasion by the breast cancer cell lines MCF-7, T47D, MDA-MB 231, and MDA-MB 468 when they were cultured alone or in the presence of a fibroblast population. Reduced invasion was associated with changes in MMP gene expression. In those tumour cells expressing MMP, there was a significant down-regulation of MMP-2 (MDA-MB 468, p<0.001), MMP-9 (MDA-MB 231, p=0.05; MDA-MB 468, p<0.001), and MT1-MMP (p<0.001 for both MDA-MB 231 and MDA-MB 468). Myoepithelial cells also caused a significant decrease in MMP gene expression in co-cultured fibroblasts. Furthermore, this was associated with reduced gelatinolytic activity as identified by zymography. This study demonstrates for the first time that primary myoepithelial cells from normal breast reduce breast cancer cell invasion and that this is mediated via modulation of both tumour cell and fibroblast function. This emphasizes the importance of the myoepithelial cell in controlling the breast microenvironment and focuses on the potential significance of the loss of this population with disease progression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3417
pubmed:author
pubmed:copyrightInfo
Copyright 2003 John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
201
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
562-72
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14648659-Antineoplastic Agents, pubmed-meshheading:14648659-Breast Neoplasms, pubmed-meshheading:14648659-Cell Line, Tumor, pubmed-meshheading:14648659-Coculture Techniques, pubmed-meshheading:14648659-Down-Regulation, pubmed-meshheading:14648659-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:14648659-Epithelial Cells, pubmed-meshheading:14648659-Female, pubmed-meshheading:14648659-Fibroblasts, pubmed-meshheading:14648659-Gelatin, pubmed-meshheading:14648659-Gene Expression Regulation, Neoplastic, pubmed-meshheading:14648659-Glyceraldehyde-3-Phosphate Dehydrogenases, pubmed-meshheading:14648659-Humans, pubmed-meshheading:14648659-Matrix Metalloproteinases, pubmed-meshheading:14648659-Muscle, Smooth, pubmed-meshheading:14648659-Neoplasm Invasiveness, pubmed-meshheading:14648659-Paracrine Communication, pubmed-meshheading:14648659-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:14648659-Tissue Inhibitor of Metalloproteinases
pubmed:year
2003
pubmed:articleTitle
Primary breast myoepithelial cells exert an invasion-suppressor effect on breast cancer cells via paracrine down-regulation of MMP expression in fibroblasts and tumour cells.
pubmed:affiliation
Breast Cancer Research Unit, Department of Pathology, University of Leicester, Glenfield Hospital, Groby Road, Leicester LE2 2BB, UK. lj17@le.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't