TY - JOUR
T1 - Augmentation of human leukemic cell invasion by activation of a small GTP-binding protein Rho
AU - Fukushima, Sachiko
AU - Yamada, Taketo
AU - Hashiguchi, Akinori
AU - Nakata, Yuji
AU - Hata, Jun ichi
N1 - Funding Information:
We thank Dr. Alan Hall (MRC LMCB, University College London, UK), Drs. Kiyoko Yoshioka and Fumio Imamura (Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan) for the gift of Rho and Rho V14 expression vectors, and Drs. Takuya Sasaki and Yoshimi Takai (Department of Molecular Biology and Biochemistry, Osaka University, Japan) for the gift of polyclonal antibody to Rho-GDS and important suggestions pertaining to these experiments. We thank Mrs. Michiko Takahashi for assistance with animal care, Mr. Hiroshi Suzuki for assistance with immunohistochemistry, Mr. Naomichi Yagi for support with electron microscopy, and Mr. Kohji Takeichi for technical photographic support. This work was supported by grants-in Aid for Pediatric research (9C-5) from the Ministry of Health and Welfare, a research grant from the Ministry of Education in Japan (05404022, 07670258, 07770163, 1770124, 11670193, 10307004), National Grant-in-Aid for the Establishment of a High-Tech Research Center in a Private University, Sankyo Foundation of Life Science, Tsumura Foundation for Medical Research, Sankyo Foundation of Life Science, and Keio Gijuku Academic Development Funds and a special grant-in-aid for innovative and collaborative research projects at Keio University.
PY - 2000/4
Y1 - 2000/4
N2 - 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.
AB - 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.
KW - Cell adhesion
KW - Invasion
KW - Leukemia
KW - Rho
KW - SCID mice
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U2 - 10.1016/S0301-472X(00)00129-6
DO - 10.1016/S0301-472X(00)00129-6
M3 - Article
C2 - 10781897
AN - SCOPUS:0034009104
VL - 28
SP - 391
EP - 400
JO - Experimental Hematology
JF - Experimental Hematology
SN - 0301-472X
IS - 4
ER -