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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)582-587
Number of pages6
JournalAnnals of Surgical Oncology
Volume10
Issue number5
DOIs
Publication statusPublished - Dec 1 2003

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Thymidine Phosphorylase
rho-Associated Kinases
Cell Movement
Messenger RNA
Polymerization
Actins
Neoplasms
Phalloidine
Neutralizing Antibodies
Oligonucleotide Array Sequence Analysis
Mitogens
Colonic Neoplasms
Transfection
Endothelial Cells
Complementary DNA

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Platelet-derived endothelial cell growth factor mediates Rho-associated coiled-coil domain kinase messenger RNA expression and promotes cell motility. / Yoshinaga, Keiji; Inoue, Hiroshi; Tanaka, Fumiaki; Mimori, Koshi; Utsunomiya, Tohru; Mori, Masaki.

In: Annals of Surgical Oncology, Vol. 10, No. 5, 01.12.2003, p. 582-587.

Research output: Contribution to journalArticle

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AU - Utsunomiya, Tohru

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N2 - 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.

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