Enhanced tumorigenicity and invasion-metastasis by hepatocyte growth factor scatter factor-met signalling in human cells concomitant with induction of the urokinase proteolysis network

被引:2
|
作者
Jeffers, M [1 ]
Rong, S [1 ]
VandeWoude, GF [1 ]
机构
[1] NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702
关键词
D O I
暂无
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector of cells expressing the Met tyrosine kinase receptor. Although HGF/SF is synthesized by mesenchymal cells and acts predominantly on epithelial cells, we have recently demonstrated that human sarcoma cell lines often inappropriately express high levels of Met and respond mitogenically to HGF/SF. In the present report we show that HGF/SF-Met signalling in the human leiomyosarcoma cell line SK-LMS-1 enhances its in vivo tumorigenicity, an effect for which the mitogenicity of this signalling pathway is likely to play a role. In addition, we found that HGF/SF-Met signalling dramatically induces the in vitro invasiveness and in vivo metastatic potential of these cells. We have studied the molecular basis by which HGF/SF-Met signalling mediates the invasive phenotype. A strong correlation has previously been demonstrated between the activation of the urokinase plasminogen activator (uPA) proteolysis network and the acquisition of the invasive-metastatic phenotype, and we show here that HGF/SF-Met signalling significantly increases the protein levels of both uPA and its cellular receptor in SK-LMS-1 cells. This results in elevated levels of cell-associated uPA and enhanced plasmin generating ability by these cells. These studies couple HGF/SF-Met signalling to the activation of proteases that mediate dissolution of the extracellular matrix basement membrane, an important property for cellular invasion-metastasis.
引用
收藏
页码:1115 / 1125
页数:11
相关论文
共 27 条
  • [21] EXPRESSION OF CONSTITUTIVELY ACTIVATED HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR-RECEPTOR (C-MET) IN B16 MELANOMA-CELLS SELECTED FOR ENHANCED LIVER COLONIZATION
    RUSCIANO, D
    LORENZONI, P
    BURGER, MM
    ONCOGENE, 1995, 11 (10) : 1979 - 1987
  • [22] CONCOMITANT EXPRESSION OF HEPATOCYTE GROWTH-FACTOR (HGF), HGF ACTIVATOR AND C-MET GENES IN HUMAN GLIOMA-CELLS IN-VITRO
    MORIYAMA, T
    KATAOKA, H
    TSUBOUCHI, H
    KOONO, M
    FEBS LETTERS, 1995, 372 (01) : 78 - 82
  • [23] Hepatocyte growth factor/scatter factor (HGF/SF) promotes adhesion (VIA alpha(4)beta(1) and alpha(5)beta(1)), migration and invasion of c-MET positive lymphoma cells
    Weimar, IS
    Muller, EJ
    Nakamura, T
    deJong, D
    deGast, GC
    Gerritsen, WR
    BRITISH JOURNAL OF HAEMATOLOGY, 1996, 93 : 1101 - 1101
  • [24] Insulinlike growth factor-I-mediated migration and invasion of human colon carcinoma cells requires activation of c-Met and urokinase plasminogen activator receptor
    Bauer, TW
    Fan, F
    Liu, WB
    Johnson, M
    Parikh, NU
    Parry, GC
    Callahan, J
    Mazar, AP
    Gallick, GE
    Ellis, LM
    ANNALS OF SURGERY, 2005, 241 (05) : 748 - 758
  • [25] Up-regulation of urokinase-type plasminogen activator and its receptor correlates with enhanced invasion activity of human glioma cells mediated by transforming growth factor-α or basic fibroblast growth factor
    Mori, T
    Abe, T
    Wakabayashi, Y
    Hikawa, T
    Matsuo, K
    Yamada, Y
    Kuwano, M
    Hori, S
    JOURNAL OF NEURO-ONCOLOGY, 2000, 46 (02) : 115 - 123
  • [26] Up-regulation of Urokinase-type Plasminogen Activator and its Receptor Correlates with Enhanced Invasion Activity of Human Glioma Cells Mediated by Transforming Growth Factor-α or Basic Fibroblast Growth Factor
    Teruaki Mori
    Tatsuya Abe
    Yukihiro Wakabayashi
    Takamitsu Hikawa
    Ken-ichi Matsuo
    Yuji Yamada
    Michihiko Kuwano
    Shigeaki Hori
    Journal of Neuro-Oncology, 2000, 46 : 115 - 123
  • [27] Targeting of urokinase plasminogen activator receptor in human pancreatic carcinoma cells inhibits c-met- and insulin-like growth factor-1 receptor-mediated migration and invasion and orthotopic tumor growth in mice
    Bauer, TW
    Liu, WB
    Fan, F
    Camp, ER
    Yang, A
    Somcio, RJ
    Bucana, CD
    Callahan, J
    Parry, GC
    Evans, DB
    Boyd, DD
    Mazar, AP
    Ellis, LM
    CANCER RESEARCH, 2005, 65 (17) : 7775 - 7781