Bone morphogenetic protein-2 suppresses invasiveness of TSU-Pr1 cells with the inhibition of MMP-9 secretion.
Bone morphogenetic protein (BMP), which is a member of the transforming growth factor beta (TGF-beta) superfamily, has powerful osteoinductive effects and various biological activities in a variety of cells. The effect of BMP-2 on the human carcinoma cell line TSU-Pr1 was examined. BMP-2 was found to inhibit the migration and invasiveness, but not the proliferation, of TSU-Pr1 cells. Gel zymography for matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) detection revealed that BMP-2 down-regulated the activity of MMP-9, but not of MMP-2 or uPA. BMP-2 also reduced the secretion of MMP-9 into the culture media, but did not affect the secretion of MMP-2, Timp-1, Timp-2 or Timp-3. These results suggest that BMP-2 inhibits migration and decreases MMP-9 secretion to suppress the invasiveness of TSU-Pr1 cells. This is the first report of a role for BMP signaling in reducing the invasiveness of cancer cells.
Department of Hygiene-Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
Toru
T
Kumagai
Takahisa
T
Shimizu
Ken
K
Takeda
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology* / Q000502:physiology; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D010959:Tissue Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9