Annals of Surgical Oncology

, Volume 10, Issue 5, pp 582–587 | Cite as

Platelet-Derived Endothelial Cell Growth Factor Mediates Rho-Associated Coiled-Coil Domain Kinase Messenger RNA Expression and Promotes Cell Motility

  • Keiji Yoshinaga
  • Hiroshi Inoue
  • Fumiaki Tanaka
  • Koshi Mimori
  • Tohru Utsunomiya
  • Masaki Mori
New Approaches to the Treatment of Hepatic Malignancies

Abstract

Background: Platelet-derived endothelial cell growth factor (PD-ECGF), whose expression is increased in several cancers, is an endothelial cell mitogen and has chemotactic activity in vitro and angiogenic activity in vivo. Tumors with high PD-ECGF expression tend to have frequent lymph node metastasis and are associated with poor outcome.

Methods: We screened genes transduced by PD-ECGF transfection to the colon cancer cell line DLD-1 by using a complementary DNA microarray. Cell motility was evaluated by in vitro migration assay. Actin fiber polymerization was visualized by immunofluorescent detection of phalloidin.

Results: Rho-associated coiled-coil domain kinase (ROCK1) was found to be significantly overexpressed in PD-ECGF transfectants compared with mock cells. PD-ECGF transfectants showed higher cell motility than mock cells. The parental cell, DLD-1, with recombinant PD-ECGF showed higher cell motility than that without recombinant PD-ECGF, in which motility was blocked by the neutralizing antibody of PD-ECGF or Y-27632, a specific inhibitor of ROCK1. Moreover, the actin fiber polymerization, which is a marker of activation of ROCK1, was higher in PD-ECGF transfectants than in mock cells.

Conclusions: PD-ECGF expression may be associated with cancer cell migration via activation of ROCK1. This may explain one mechanism by which tumors with high expression of PD-ECGF show aggressive behavior.

Key Words

PD-ECGF ROCK1 Cell motility cDNA microarray 

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Copyright information

© The Society of Surgical Oncology, Inc. 2003

Authors and Affiliations

  • Keiji Yoshinaga
    • 1
  • Hiroshi Inoue
    • 1
  • Fumiaki Tanaka
    • 1
  • Koshi Mimori
    • 1
  • Tohru Utsunomiya
    • 1
  • Masaki Mori
    • 1
    • 2
  1. 1.Department of Molecular and Surgical OncologyMedical Institute of Bioregulation, Kyushu UniversityBeppuJapan
  2. 2.Department of Molecular and Surgical OncologyMedical Institute of Bioregulation, Kyushu UniversityBeppuJapan

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