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NEW APPROACHES TO THE TREATMENT OF HEPATIC MALIGNANCIES |
From the Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Correspondence: Address correspondence and reprint requests to: Masaki Mori, MD, PhD, Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumibaru, Beppu, 874-0838, Japan; Fax: 81-977-27-1651; E-mail: mmori{at}beppu kyushu-u.ac.jp.
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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