{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:26:16Z","timestamp":1771464376577,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2003,10,31]],"date-time":"2003-10-31T00:00:00Z","timestamp":1067558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2003,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In normal breast and ductal carcinoma\n                    <jats:italic>in situ<\/jats:italic>\n                    , 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\u2013basement 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\u2010ductal 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\u2010PCR with ELISA quantitation, with zymographic analysis to measure enzyme activity. Normal breast myoepithelial cells significantly reduced invasion by the breast cancer cell lines MCF\u20107, T47D, MDA\u2010MB 231, and MDA\u2010MB 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\u2010regulation of MMP\u20102 (MDA\u2010MB 468,\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001), MMP\u20109 (MDA\u2010MB 231,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.05; MDA\u2010MB 468,\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001), and MT1\u2010MMP (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001 for both MDA\u2010MB 231 and MDA\u2010MB 468). Myoepithelial cells also caused a significant decrease in MMP gene expression in co\u2010cultured 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. Copyright \u00a9 2003 John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.1483","type":"journal-article","created":{"date-parts":[[2003,12,2]],"date-time":"2003-12-02T09:23:54Z","timestamp":1070357034000},"page":"562-572","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Primary breast myoepithelial cells exert an invasion\u2010suppressor effect on breast cancer cells via paracrine down\u2010regulation of MMP expression in fibroblasts and tumour 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