RT Journal Article
SR Electronic
T1 Role of the Plasminogen Activator and Matrix Metalloproteinase Systems in Epidermal Growth Factor- and Scatter Factor-stimulated Invasion of Carcinoma Cells
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 5221
OP 5230
VO 58
IS 22
A1 Rosenthal, Eben L.
A1 Johnson, Timothy M.
A1 Allen, Edward D.
A1 Apel, Ingrid J.
A1 Punturieri, Antonello
A1 Weiss, Stephen J.
YR 1998
UL http://cancerres.aacrjournals.org/content/58/22/5221.abstract
AB Normal as well as neoplastic cells traverse extracellular matrix barriers by mobilizing proteolytic enzymes in response to epidermal growth factor (EGF)-EGF receptor (EGFR) or hepatocyte growth factor/scatter factor (SF)-c-Met interactions. The plasminogen activator-plasminogen axis has been proposed to play a key role during cell invasion, but the normal development of plasminogen activator- as well as that of plasminogen-deficient mice supports the existence of alternate proteolytic systems that permit cells to traverse extracellular matrix barriers. To characterize the role that matrix-degrading proteinases play in EGF- or SF-stimulated invasion, a human squamous carcinoma cell line (UM-SCC-1) was triggered atop the matrices of type I collagen or human dermal explants in a three-dimensional culture system. During EGF- or SF-induced invasion, UM-SCC-1 cells expressed urokinase-type plasminogen activator (uPA) and uPA receptor as well as the matrix metalloproteinases (MMPs), membrane-type MMP-1, collagenase 1, stromelysin 1, and gelatinase B. Despite the presence of a positive correlation between uPA receptor-uPA expression and growth factor-stimulated invasion, UM-SCC-1 invasion was not affected by inhibitors directed against the plasminogen activator-plasminogen axis. In contrast, both recombinant and synthetic MMP inhibitors completely suppressed invasion by either EGF- or SF-stimulated cells without affecting either proteinase expression or cell motility across collagen-coated surfaces. These data demonstrate that MMPs, but not the plasminogen activator-plasmin system, can directly regulate the ability of either EGF- or SF-stimulated tumor cells to invade interstitial matrix barriers. ©1998 American Association for Cancer Research.