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

Autor: J. L. Jones, Rosemary A. Walker, J H Pringle, Jacqueline A Shaw
Rok vydání: 2003
Předmět:
Zdroj: The Journal of Pathology. 201:562-572
ISSN: 1096-9896
0022-3417
DOI: 10.1002/path.1483
Popis: 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
Databáze: OpenAIRE