Augmentation of human leukemic cell invasion by activation of a small GTP-binding protein Rho.
OBJECTIVE
The functions of a small GTP-binding protein, Rho, in human leukemic cell invasion was investigated in vivo and in vitro.


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.


CONCLUSIONS
Results suggest that Rho activation accelerates human leukemic cell invasion via augmentation of cell adhesion.
Fukushima
S
S
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Yamada
T
T
Hashiguchi
A
A
Nakata
Y
Y
Hata
J
J
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002051:Burkitt Lymphoma / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D017254:Leukemic Infiltration / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008871:Microvilli / Q000648:ultrastructure; D016297:Mutagenesis, Site-Directed; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D013116:Spinal Cord / Q000473:pathology; D013154:Spleen / Q000473:pathology; D014407:Tumor Cells, Cultured; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D018809:Proliferating Cell Nuclear Antigen; D020741:rho GTP-Binding Proteins