Abstract
Hepatocyte growth factor (HGF) was suggested to play an important role in the regulation of mitogenesis, motogenesis, angiogenesis, migration and invasion for various types of cells, and acts through a specific membrane receptor encoded by c-met proto-oncogene. However, the mechanism of the effect of HGF on tumor invasion of prostate cancer cells remains unclear. We investigated the effect of HGF on the invasion of PC-3 and DU-145 prostate cancer cells through a reconstituted basement membrane (Matrigel), the haptotactic migration to fibronectin substrate, the expression of protein and mRNA for matrix metalloproteinases (MMP)-1 and -9, membrane-type 1-MMP (MT1-MMP), urokinase-type plasminogen activator (u-PA) and its receptor (uPAR). HGF increased both Matrigel invasion and haptotactic migration of prostate cancer cells. Furthermore, HGF also increased the production of MMP-1 and -9, MT1-MMP, u-PA and uPAR of these cells. These results suggested that HGF increased the invasive potential of prostate cancer cells probably through enhancement of cell motility and the production of MMPs and u-PA.
MeSH terms
-
Antineoplastic Agents / metabolism
-
Cell Adhesion / drug effects
-
Cell Movement / drug effects
-
Collagen
-
Drug Combinations
-
Fibrin / metabolism
-
Hepatocyte Growth Factor / pharmacology*
-
Humans
-
Laminin
-
Male
-
Matrix Metalloproteinase 1 / genetics
-
Matrix Metalloproteinase 1 / metabolism
-
Matrix Metalloproteinase 9 / genetics
-
Matrix Metalloproteinase 9 / metabolism
-
Neoplasm Invasiveness
-
Prostatic Neoplasms / enzymology
-
Prostatic Neoplasms / pathology*
-
Proteoglycans
-
Proto-Oncogene Mas
-
RNA, Messenger / metabolism
-
RNA, Neoplasm / genetics
-
Receptors, Cell Surface / genetics
-
Receptors, Cell Surface / metabolism
-
Receptors, Urokinase Plasminogen Activator
-
Recombinant Proteins / pharmacology
-
Reverse Transcriptase Polymerase Chain Reaction
-
Tissue Inhibitor of Metalloproteinase-1 / genetics
-
Tissue Inhibitor of Metalloproteinase-1 / metabolism
-
Tumor Cells, Cultured
-
Urokinase-Type Plasminogen Activator / genetics
-
Urokinase-Type Plasminogen Activator / metabolism
Substances
-
Antineoplastic Agents
-
Drug Combinations
-
Laminin
-
MAS1 protein, human
-
PLAUR protein, human
-
Proteoglycans
-
Proto-Oncogene Mas
-
RNA, Messenger
-
RNA, Neoplasm
-
Receptors, Cell Surface
-
Receptors, Urokinase Plasminogen Activator
-
Recombinant Proteins
-
Tissue Inhibitor of Metalloproteinase-1
-
matrigel
-
Hepatocyte Growth Factor
-
Fibrin
-
Collagen
-
Urokinase-Type Plasminogen Activator
-
Matrix Metalloproteinase 9
-
Matrix Metalloproteinase 1