Augmentation of human leukemic cell invasion by activation of a small GTP-binding protein Rho

Sachiko Fukushima, Taketo Yamada, Akinori Hashiguchi, Yuji Nakata, Jun ichi Hata

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objective. The functions of a small GTP-binding protein, Rho, in human leukemic cell invasion was investigated in vivo and in vitro. Materials and Methods. Human leukemic KM3 and Reh cells (derived from B-cell-type common acute lymphoid leukemias) were inoculated into severe combined immundeficiency (SCID) mice. Alteration of invasion in SCID mice inoculated with KM3 cells that were introduced with the expression vector for Rho Val14 (Rho V14), an activated mutant form of Rho, was observed. Results. SCID mice inoculated with KM3 and Reh cells developed paraplegia 21 days after inoculation. All died by day 26-27. The leukemic cells were localized to bone marrow and around the spinal cord, with no infiltration into peripheral blood, spleen, liver, thymus, or lymph nodes. SCID mice inoculated with Rho V14-transfected KM3 cells showed a 5-day reduction in the time to paraplegia and death compared with SCID mice inoculated with hygromycin-resistance gene-transfected KM3 (hyg(r)) cells. In addition, the mice inoculated with Rho V14 cells showed leukemic cell infiltration, not only into bone marrow and around the spinal cord but also into peripheral blood, liver, and spleen. There were no in vitro or in vivo differences in growth rates of Rho V14 and hyg(r) cells. However, the Rho V14 cells showed markedly increased cell adhesion compared to the hyg(r) cells. Conclusion. Results suggest that Rho activation accelerates human leukemic cell invasion via augmentation of cell adhesion. Copyright (C) 2000 International Society for Experimental Hematology.

Original languageEnglish
Pages (from-to)391-400
Number of pages10
JournalExperimental Hematology
Volume28
Issue number4
DOIs
Publication statusPublished - 2000 Apr 1

Keywords

  • Cell adhesion
  • Invasion
  • Leukemia
  • Rho
  • SCID mice

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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