Breast cancer cell-derived EMMPRIN stimulates fibroblast MMP2 release through a phospholipase A(2) and 5-lipoxygenase catalyzed pathway.
Metalloproteinases (MMP) produced by both cancer and normal stromal fibroblast cells play a critical role in the metastatic spread of tumours, however little is known of the regulation of their release. In this report we demonstrate that breast cancer cells in culture release apparently full length soluble EMMPRIN that promotes the release of pro-MMP2 from fibroblasts. The generation of MMP2 is mediated by activation of phospholipase A(2) and 5-lipoxygenase. These results suggest that the production of soluble EMMPRIN, phospholipase A(2) and 5-lipoxygenase activities are sites for potential therapeutic intervention.
Taylor
Paul M
PM
Cancer Research UK Institute for Cancer Studies, Birmingham University, Birmingham, B15 2TT, UK.
Woodfield
Richard J
RJ
Hodgkin
Matthew N
MN
Pettitt
Trevor R
TR
Martin
Ashley
A
Kerr
David J
DJ
Wakelam
Michael J O
MJ
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology*; D051926:Basigin; D001943:Breast Neoplasms / Q000378:metabolism*; D002384:Catalysis; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000502:physiology*; D010741:Phospholipases A / Q000502:physiology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C497886:BSG protein, human; D008562:Membrane Glycoproteins; D051926:Basigin; D001094:Arachidonate 5-Lipoxygenase; D010741:Phospholipases A; D020778:Matrix Metalloproteinase 2